AU2007203561A1 - Method for identifying metastatic tumor cells - Google Patents

Description

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION Standard Patent Applicants: FORSCHUNGSZENTRUM KARLSRUHE GMBH Invention Title: METHOD FOR IDENTIFYING METASTATIC TUMOR CELLS The following statement is a full description of this invention, including the best method for performing it known to us: la Method for identifying metastasizing tumor cells The present invention relates to a method for MH identifying metastasizing tumor cells and to the identification of compounds for treating tumors.

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I In higher organisms, differential gene expression regulates cell growth or organogenesis in a complex manner. In particular, because of its great relevance to medicine, the elucidation of the molecular Ci mechanisms which are involved in the development of tumor cells is the subject of intensive investigations.

However, the processes which are involved in the development of an invasive tumor from primary tumor tissue (metastasis formation) are less well investigated. It is known that some basic conditions have to be created to enable tumors to invade. These conditions relate to changes in the microenvironment of the cells, i.e. proteolysis of the cells, and to changes in adhesion properties and migration. Thus far, it has only been possible to identify a small number of genes which are expressed differentially during progression of the tumor. Some protease genes, such as uPa or matrix metalloproteases (MMP) may be mentioned by way of example (Matrisian L.M. et al., 1990, Curr.

Top. Dev. Biol., 24: 219-259 and Matrisian,

L.M.,

Bioessays, 1992, 14: 455-463). Various integrins (Riuz P. et al., 1993, Cell. Adhes. Commun., 1: 67-81), or what is termed the lymphocyte-homing receptor CD44 (Ponta et al., Frontiers in Bioscience, 1998, 3: 650- 656), are known with regard to the adhesive properties.

However, the number and identity of the genes which are involved in the metastatic process are to a large extent still unknown. However, in order to obtain an improved understanding of the processes involved in 2 tumor progression, it is necessary to clearly identify ¢C as large a number of metastasis-specific genes as possible.

In addition, there has thus far not been any suitable system available which, with justifiable expense and \O adequate reliability, makes it possible to draw conclusions with regard to cancer cell status and the O probable existence of a tumor metastasis.

The present invention relates to a method for identifying metastasizing tumor cell-s- ,--with at least one cDNA sequence, which is selected from a population in accordance with Figures A and/or B, or corresponding complete gene sequences which are derived therefrom, or functional fragments thereof, or their homologs or alleles, being used as markers for hybridizing with tumor tissue.

The present invention also encompasses the gene products (polypeptides) which are derived from the cDNA sequences which are selected from a population in accordance with Figures A and/or B or from the corresponding complete gene sequences, or functional fragments thereof or their homologs or alleles.

According to the invention, the gene products also include the isoforms of these polypeptides which, while having an amino acid sequence which is altered still have the same effect as far as their function is concerned.

The invention furthermore also relates to antibodies which bind specifically to the previously mentioned gene products and which are prepared using the abovementioned cDNA sequences and/or their gene products.

-3- According to the invention, the complete gene sequences also include, in addition to the coding nucleotide sequences, the appurtenant regulatory regions upstream and downstream of the coding regions. The regulatory regions are to be understood as being functional structures such as promoters, terminators, target INO sequences, retention signals, translation enhancers, In Ssplicing elements and polyadenylation signals.

According to the invention, a functional fragment is a O nucleotide sequence which encodes a corresponding polypeptide which, for its part, exhibits a specific activity of the corresponding whole-length protein. In addition, a functional fragment is to be understood, according to the invention, as being a nucleotide sequence which leads, under stringent conditions, to a specific hybridization signal. In this context, the length of the functional fragment can vary in a range from at least 10 up to several hundred nucleotides. The same applies to a functional fragment of an encoded protein, the length of which fragment can vary in a range from at least 10 to 250 amino acids.

According to the invention, homologs are to be understood as being complementary nucleotide sequences or nucleotide sequences which hybridize with the cDNA sequences which are selected from a population according to Fig. A and/or B or complete gene sequences which are derived therefrom or functional gene fragments. Hybridizing sequences include similar sequences which are selected from the group of DNA or RNA which interact specifically, under stringent conditions, with the cDNA sequences according to the invention. A preferred, but not limiting, example of stringent hybridization conditions is hybridization in 6x sodium chloride/sodium citrate buffer (SSC) at 45 0

C

followed by one or more washing steps in 0.2x SSC, 0.1% SDS at 65 0

C.

4 u Alleles are sequences which, despite having a nucleotide sequence which differs, still possess the desired functions, that is are functionally equivalent.

Functional equivalents consequently include naturally occurring variants of the sequences described herein NO and also artificial nucleotide sequences, e.g.

Snucleotide sequences which are obtained by chemical O synthesis and which are matched to the codon usage of the organism.

A functional equivalent (allele) is also understood, in particular, as meaning natural or---art-i-f-icial mutations of the originally isolated gene sequences or of the corresponding complete gene sequences, or of their homologs which encode polypeptides involved in tumor metastasis, which still exhibit the desired function.

Mutations comprise substitutions, additions, deletions, exchanges or insertions of one or more nucleotide residues. Mutations can give rise both to functional changes in the regulatory regions of a gene and to a protein whose activity is altered.

Consequently, the present invention also encompasses, for example, those nucleotide sequences which are obtained by modifying the cDNA sequences according to the invention or their complete gene sequences or functional fragments thereof, or their homologs. The aim of such a modification can, for example, be that of further delimiting the coding sequence or else, for example, be that of inserting further restriction enzyme cleavage sites. Functional equivalents are also those variants in which the regulatory regions are altered resulting, for example, in gene expression being attenuated or augmented as compared with the initial gene or initial gene fragment.

According to the invention, the nucleotide sequences encoding metastasis-specific polypeptides or their 5 O isoforms can be natural, chemically synthesized, cN modified or artificially produced nucleotide sequences.

Furthermore, the previously mentioned nucleotide sequences can consist of heterologous nucleotide sequences and are mixtures of the previously described nucleotide sequences. In addition to this, functionally k\ equivalent sequences also include those which possess a nucleotide sequence which has been altered and which confers an altered activity, which may be attenuated or augmented, on the gene product which is encoded by it.

In addition, the invention relates to artificial nucleotide sequences as long as they, as described above, impart the desired properties. These artificial nucleotide sequences can, for example, be obtained by "back-translating" proteins which have been constructed by molecular modeling, or by means of in-vitro selection. Coding nucleotide sequences which are obtained by back-translating a polypeptide sequence in accordance with the codon usage which is specific for humans are particularly suitable. A skilled person who is familiar with recombinant methods can readily determine the specific codon usage by carrying out computer analyses of other known genes.

According to the invention, the previously mentioned cDNA sequences are isolated from defined rat adenocarcinoma systems. In a preferred embodiment of the present invention, the adenocarcinoma system is the rat tumor system 13762NF (mammary carcinoma; Neri et al., JNCI, 1982, Vol. 68 507-517) The cell line MTPa was selected as a nonmetastisizing cell line.

According to the invention, the metastasizing cell line is represented by the cell line MTLY. The rat pancreas carcinoma system Bsp73, together with the cell lines 1AS or 10AS and ASML represent another system which is preferred in accordance with the invention (Matzku et al., Invasion Metastasis, 1983, 109-123). The cell 6 lines G-subline and, respectively, AT-1, AT-3, MatLu CI and MatLyLu, as nonmetastasizing and, respectively, Smetastasizing cell lines, are mentioned as an example of a rat prostate carcinoma system (Isaacs et al., Prostate, 1986, 261-281). However, this choice is not limiting for the present invention; on the O contrary, it also includes the use of other suitable cell lines or carcinoma systems.

10 A crucial advantage of using rat cell lines is that, in Svivo, the metastatic cells exhibit a metastasizing behavior which is analogous to that--e-. human cancer cells (Neri et al., Int. J. Cancer, 1981, 28: 731-738; Matzku et al., Invasion Metastasis, 1983, 3: 109-123).

In addition to this, the cell lines are simpler to manipulate than human tumor tissue. Furthermore, as compared with human tumor tissue, using defined rat cell lines offers the advantage that the results are highly reproducible. In particular, in this system, there is the possibility of genetically altering cell lines and investigating, in test systems, the properties which have been acquired or lost.

Furthermore, simple transfer to syngenic animals is possible whereas, because of interfering immune responses, human tumor tissue would have to be transferred to an elaborate artificial system of an immunodeficient recipient. In addition to this, some hybridizations using human mammary carcinoma cell lines were also carried out. For example, the cell lines MDA- MB231 and MDA-MB-468 (Cailleau et al., J. Natl. Cancer Inst., 1974, 661-674 and Cailleau et al., In Vitro, 1978 911-915) which have been used were employed, inter alia, in order to demonstrate, for example by means of cross-hybridizations, that the "rat sample" employed is suitable for analyzing human tumor material.

7 Methods which are known per se are used for identifying c the large number, according to the invention, of Sdifferentially expressed transcripts of metastasisspecific genes. Mention should be made here of SSH (subtractive suppression hybridization; Diatchenko et al., Proc. Natl. Acad. Sci., 1996, 93: 6025-6030) k\ difference analysis, which is particularly suitable for c identifying rare transcripts, and of an effective O afterselection method, which follows it and which is characterized by high sample throughput and a high Sdegree of reliability and which virtually rules out selecting falsely positive or falsely negative clones (von Stein et al., Nucleic Acids Research, 1997, 2598-2602) Northern blot analyses and RT-PCR analyses are other methods of choice which should be mentioned for determining, in accordance with the invention, the metastasis-specific expression of selected cDNA clones, for the purpose of identifying metastasizing tumor cells, which methods do not, however, have a limiting effect on the present invention.

In this connection, a special embodiment of the method according to the invention comprises the following steps: A) making a PCR-based subtractive cDNA gene library proceeding from total mRNA populations derived from metastasizing and nonmetastasizing tumor cells, B) identifying a population of different cDNA clones in which each cDNA sequence represents an individual (potential) metastasis-specific gene, C) constructing the complete gene sequence on the basis of these cDNA clones, D) preparing a sense RNA probe and an antisense RNA probe starting with at least one sequence which is selected from this cDNA population or the corresponding complete gene sequences which are 8 derived therefrom, in particular from a population CI in accordance with Figures A and/or B, E) making suitable thin layer preparations of the tumor material to be investigated, F) hybridizing the tumor material to be investigated in situ with the previously mentioned sense and k\ antisense RNA probes, and G) identifying metastasizing tumor cells by detecting O positive hybridization products.

010 In another embodiment of the present invention, marker genes which are involved in the-- met-a-tasis of tumor cells are identified by the steps of a) making a PCR-based subtractive cDNA gene library proceeding from total mRNA populations derived from metastasizing and nonmetastasizing tumor cells, b) identifying a population of different cDNA clones in which each cDNA sequence represents an individual (potential) metastasis-specific gene, c) constructing the complete gene sequence on the basis of these cDNA clones, d) cloning the cDNA and/or complete gene sequence into an expression vector both in the sense reading direction and the antisense reading direction, e) transferring and subsequently expressing this/these vector(s) into and in nonhuman mammalian cell lines, preferably rat cell lines, f) validating the involvement in the metastasis of tumor cells of the genes identified in step b) by indentifying invasive tumors.

In addition, the method according to the invention for identifying metastasizing tumor cells is characterized by the fact that at least one cDNA sequence selected from a population in accordance with Fig. B is involved in the metastasis of pancreas tumor tissue while at 9 least one cDNA sequence selected from a population in I accordance with Fig. A is involved in the metastasis of breast tumor tissue.

C 5 An essential feature of the present invention is the provision of an exceptionally large population of different cDNA clones which are representative of a correspondingly large number of different, i.e.

O individual, metastasis-specific genes such that it is possible to carry out a molecular typing of the different clinical manifestations of a cancer disease with a high degree of reliability. In the same way, it is possible to draw conclusions with regard to case control, i.e. the cancer cell stage of the different manifestations, and, in particular, with regard to the potential of the tumor tissue being investigated for metastasizing.

The present invention consequently makes available a multiplicity of potential marker sequences, marker genes and/or corresponding proteins for identifying and/or treating invasive tumor cells and/or tumor tissues or cells and/or tissues which have a high potential for metastasizing.

In another embodiment of the present invention, the method according to the invention is characterized in that the cDNA sequences in accordance with Fig. C are preferably suitable for use as markers for identifying metastasizing human breast and/or colon tumor tissue.

In this connection, reference may, by way of example, be made, in particular, to the sequences which are designated CD 24 and S7 in Fig. C and which exhibited the best crosshybridization results with human tumor tissue. CD 24 is a differentiation-specific protein which appears during the maturation of B lymphocytes and T lymphocytes (Fischer G.F. et al., 1990, J.

Immunol., 144: 638-641). It is possible to use CD 24 10 mRNA to detect metastasizing human colon tissue. The main task of the ribosomal protein S7 is that of ensuring that 165 RNA folds correctly (Wimberley, B.T.

et al., 1997, Structure, 5: 1187-1198). It has not previously been known that S7 is involved in tumor progression. Consequently, the present invention is making available, in the form of S7 mRNA, a novel tumor marker for metastasizing breast cell tissue. Lymph node tissue metastases which originate from an invasive breast cell carcinoma are indicated by an increase in the expression of both these tumor markers.

Fig. D presents a comparison of the expression of genes and tumor-associated molecules in cell lines which differ in their metastatic potential. Fig. E shows the results of the in-situ hybridizations.

The unambiguous identification, according to the invention, of cDNA clones which are involved in the metastasis of tumor tissue makes it possible, in a simple manner, both to carry out an extensive cloning of the complete genes and to carry out a functional analysis of the genes which are involved, in humans, in the expression of a metastatic phenotype. At the same time, this opens up the possibility of investigating a large number of metastasis-specific regulatory sequences. The insights which are obtained will be very helpful, particularly in connection with the further elucidation of molecular mechanisms for regulating the formation of metastases by tumors.

The findings of the present invention are furthermore suitable for improving the diagnosis of cancer diseases, in particular the typing of the cancer cell stage, and, following on from that, developing more efficient options for therapy. In order to treat tumor diseases, it is possible to conceive of deriving complementary (antisense) mRNA sequences, in particular 11 Q short oligonucleotides, from the previously mentioned cDNA sequences and then posttranscriptionally decreasing or preventing the expression of metastasisspecific genes by introducing these antisense mRNA sequences into tumor cells. It is furthermore possible to conceive of a tumor disease treatment in which the \O function of metastasis-specific polypeptides is impeded Sor blocked, at the posttranslational level, by substances or ligands being specifically bound to the polypeptides, thereby decreasing or preventing metastasis of the tumor.

(N

The present invention also relates to a method for identifying compounds for treating tumors, with a metastasis-specific gene sequence, which is derived from at least one of the cDNA sequences selected from a population in accordance with Fig. A and/or B, being expressed in nonhuman mammalian cells, for example rat cell lines, chemically, biologically and/or pharmaceutically active compounds, such as proteins, peptides or low molecular weight compounds, being incubated with the previously mentioned cells, and those compounds which exhibit a modulating effect on the expression of the genes which are associated with the tumor metastasis, or on the activity of the proteins which are encoded by the genes, being subsequently selected. It is then possible to conceive of using these compounds to produce compositions which can be used for treating tumors.

According to the invention, a modulating effect is to be understood as meaning an augmentation or an attenuation. According to the invention, this encompasses an interactive inhibition within the cells as well as regulatory interaction on the cell surface.

The metastasis-specific gene sequences according to the invention can, for example, be introduced into, and 12 expressed in, the nonhuman mammalian cells using a CI suitable recombinant vector which contains at least one gene sequence according to the invention which is derived from a cDNA sequence selected from a population C 5 in accordance with Fig. A and/or B, or complete gene sequences or functional fragments thereof, for example O coding sequences, and, in addition, regulatory 3 nucleotide sequences, in particular from the group comprising promoters, terminators, target sequences, retention signals and translation enhancers, splicing elements, polyadenylation signals or resistancemediating nucleotide sequences and--nuc-eotide sequences for replication in the relevant target cell or integration into its genome.

The present invention further relates to a measuring system for identifying compounds for treating tumors, which system contains at least one gene which is associated with tumor metastasis and which is obtained using a cDNA sequence in accordance with Fig. A and/or B, or alleles or homologs thereof, and at least one chemically, biologically and/or pharmaceutically active compound.

This measuring system according to the invention provides the possibility of carrying extensive regulatory studies and binding studies with the primary aim of establishing whether and, where appropriate, in which ranges, the compound exerts an effect on expression of the gene, i.e. attenuates or augments this expression. The measuring system which is employed in accordance with the invention can, for example, be a nonhuman mammalian cell, preferably a defined rat cell line.

Another variant of the present invention relates to a measuring system which contains at least one tumor metastasis-related protein, or isoforms thereof, which is/are encoded by a gene sequence, or its homologs, 13 which is/are obtained from a cDNA sequence in accordance with Fig. A and/or B, and also at least one chemically, biologically and/or pharmaceutically active compound. In this case, too, the measuring system S according to the invention provides the possibility of carrying out extensive regulatory studies and binding k)studies with the primary aim of establishing whether and, where appropriate, in what ranges, the compound O binds to a tumor metastasis-associated protein and 10 alters, i.e. attenuates or augments, the activity of this protein.

The present invention furthermore relates to the compounds themselves and/or their use for producing compositions which are intended for treating tumor diseases and which comprise compounds which have been identified by a previously described method or using a previously described measuring system.

In addition, the present invention relates to cDNA sequences which are selected from a population in accordance with Fig. A and/or B or complete gene sequences which are derived therefrom, or their homologs, or functionally equivalent sequences, for use in one of the previously described methods or measuring systems. This also includes the use of mixtures of the cDNA sequences according to the invention.

The present invention also relates to the gene products (polypeptides) which can be prepared, or derived therefrom, using the cDNA sequences according to the invention.

In the same way, the present invention relates to genetically altered nonhuman mammalian cells which contain at least one cDNA sequence according to the invention which is selected from a population in accordance with Fig. A and/or B, or complete gene sequences which are derived therefrom, or functional 14 Sfragments, or the homologs or alleles, or a recombinant Cl vector of the previously described type, or gene products of the abovementioned type.

The present invention furthermore encompasses antibodies which bind specifically to said gene products according to the invention, with it being possible to prepare these antibodies using the cDNA sequences and/or gene products according to the invention.

cl The invention furthermore uses a probe-f-or specifically hybridizing with tumor tissue, with this probe being prepared from a cDNA sequence which is selected from a population in accordance with Fig. A and/or B, or from complete gene sequences which are derived therefrom, or their homologs or functionally equivalent sequences, and with the probe containing a label which is suitable for detection purposes and which is preferably not radioactive, and/or the probe being 30 nucleotides, preferably 15-20 nucleotides, particularly preferably nucleotides, in length.

The present invention furthermore relates to a test kit which contains at least one cDNA sequence which is selected from a population accordance with Fig. A and/or B, or complete gene sequences which are derived therefrom, or functional gene fragments thereof, or their homologs or alleles, an instruction for preparing a previously described probe and also instructions for hybridizing and detecting nucleotide sequences in tumor tissue. Preference is given to using a mixture of several relevant cDNA sequences.

The present invention furthermore relates to the use of compounds, which have been identified by a method according to the invention and/or using a measuring system according to the invention, for producing 15 compositions which can be used for treating tumors. In CI the same way, the present invention encompasses the use of the antibodies according to the invention for producing compositions which can be used for treating tumors. In addition, the cDNA sequences according to the invention, gene products, antibodies and/or parts thereof, and/or the compounds according to the invention which are involved in the development of tumor metastases, are suitable for being used in areas of tumor metastasis diagnosis and/or tumor metastasis Stherapy. In areas of tumor diagnosis, for example, this I also includes identifying further tumor metastasis markers of human origin.

The present invention is characterized in more detail by the following implementation examples which do not, however, have a limiting effect on the invention: General methods The isolation and analysis of nucleic acids, general cloning techniques, DNA sequencing, RNA techniques, and methods for transferring and hybridizing nucleic acids, are described in Sambrook et al., Molecular cloning: A laboratory manual, 1989, Cold Spring Harbour Laboratory Press, as are general procedures for culturing cells and histological techniques.

Subtractive cloning of differentially expressed genes

(SSH)

The preparation of a differential cDNA library (subtraction library) in accordance with the principle of what is termed suppressive subtractive hybridization is described in Diatchenko L. et al., 1996, Proc Natl Acad Sci USA, 93: 6025-6030. The subtraction reaction was effected using the CLONTECH PCR-Select cDNA Subtraction kit from Clontech Laboratories, Palo Alto, USA, in accordance with the manufacturer's instructions.

16

C

0 Analysis of the cDNA clones of the subtraction library, Staking as an example the rat cell line 13762 In order to use a southern blot analysis to test the efficiency of the subtraction, it is necessary to prepare amplified RsaI fragments of the driver, MTPa, 0 since the subtracted library, ML, also consists of RsaI-digested cDNA fragments. After the MTPa cDNA had O been digested with RsaI, adaptors (Eco linkers) were 1 10 ligated to the fragments, which were then amplified Susing the corresponding PCR primers (Eco linker primers) in accordance with the condit-iens for the 2nd SSH PCR. MTLY was used in the form of the Ic tester fraction (see SSH manual).

Ligating into a TA vector The PCR products from the 2nd SSH PCR round were ligated into a TA vector (pCRII.1, Invitrogen). Cloning an insert into the pCR.II.1 vector interrupts the coding sequence of the P-galactosidase gene, which means that it is possible to distinguish recombinant clones (white) from empty vectors (blue). However, since the Tag polymerase which is used possesses proofreading activity, it is necessary to incubate the PCR products in a further step, after a preceding phenol/chloroform extraction, with dATP and another Taq DNA polymerase (Eurobio Taq polymerase) at 72 0 C for min and then perform another phenol chloroform extraction. The ligation was effected using the T4 DNA ligase (Invitrogen), which is enclosed with the vector, in a ratio of 1:1 (for each 25 ng of vector and subtracted library).

Transforming into electrocompetent bacteria and blue/white sorting The library which was ligated in the pCRII.1 vector was transformed into electrocompetent bacteria (ELEKTROMAX, strain DH10B, Invitrogen) and the bacteria were plated 17 out on 15 cm bacterial dishes. In addition to LB agar, CI the dishes contained the selection antibiotic Sampicillin (100 yg/ml) and also 100 pM IPTG and X-Gal (50 ig/ml) for blue/white sorting. The bacterial dishes were incubated at 37 0 C until small colonies were visible. In order to make it easier to distinguish O between white and blue colonies, the plates were kn subsequently incubated at 4 0

C.

10 Picking clones and colony PCR

S

A total of 1985 clones were picked by the blue/white selection procedure and transferred to sterile 96-well microtiter plates which contained LB medium and ampicillin (100 pg/pl) The bacteria were allowed to grow in these plates at RT for 14 hours while being shaken gently. In order to implement the colony PCR, il of each bacterial culture were removed, using a multichannel pipette, and transferred to a 96-well PCR plate and mixed, on this latter plate, with in each case 90 il of sterile water. For denaturing, the plate was incubated at 95 0 C for 5 min. in the PCR machine (Perkin-Elmer 9600 thermal cycler). A multichannel pipette was then used to transfer 5 1p of each lysate into a second 96-well PCR plate into which in each case 90 pl of the PCR mixture had been introduced. The cDNA fragments were amplified using the subtraction nested primers 1 and 2.

PCR mixture (50 1l assay): 0.5 U of Taq polymerase (Promega), 5 l of buffer (Promega), 200 AM dNTPs, in each case 10 pmol of the nested primers 1 and 2 of the subtraction reaction 5 1p of the bacterial lysate PCR conditions: 94 0 C, 30 seconds 68 0 C, 30 seconds 72 0 C, 30 seconds 18 Reverse northern blot analysis CI A reverse northern blot analysis was used to test which Sclone did indeed contain differentially expressed cDNA fragments. For this, the amplified cDNA fragments c 5 (colony PCR) were loaded in identical order onto 2 high-density agarose gels (Centipede TM gel electrophoresis chambers, Owl Scientific, Woburn, USA) 2 x 96 samples (2 microtiter plates) were loaded per O gel. In this connection, it is of the greatest 10 importance that both the gels are loaded exactly Sequally. In each case, a GAPDH control was loaded onto the last position for the purpose--of subsequently quantifying .the signal strength. After alkaline blotting (see southern blot analysis), the membrane duplicates were hybridized with 32 P-labeled tester (MTLY) cDNA or driver (MTPa) cDNA (in each case digested with RsaI) and analyzed by autoradiography.

Preparing hybridization probes from the isolated cDNA fragments In order to prepare the probes, the cDNA fragments were amplified from the corresponding bacterial clones, following the principle of colony PCR, using the subtraction nested primers 1 and 2.

PCR mixture (50 yl assay): U of Taq polymerase (Promega), 5 41 of buffer (Promega), 200 yM dNTPs, in each case 10 imol of the nested primers 1 and 2 of the subtraction reaction 5 1p of the bacterial lysate PCR conditions: 94 0 C, 30 seconds 680C, 30 seconds 720C, 30 seconds The cDNA fragments which were obtained, and which were differentially expressed, are collected in Fig. A and Fig. B, with Fig. A representing cDNA fragments obtained from a mammary carcinoma-specific library 19 (MLSSH) and Fig. B representing cDNA fragments obtained (C from a pancreas-specific library (PLSSH).

Description of the figures c Fig. A: List of the cDNA sequences contained in the mammary carcinoma-specific library which were obtained by Ssuppressive substractive hybridization (MLSSH) Fig. B: List of the cDNA sequences contained in the pancreasspecific library which were obtained by suppressive substractive hybridization (PLSSH).

Fig. C: cDNA sequences of CD 24 and S7, as tumor markers for invasive human breast tumor tissue and/or colon tumor tissue.

Fig. D: Comparison of the expression of novel genes and tumorassociated molecules in cell lines having different metastatic potential. The figure consists of northern blots from four different rat tumor systems and two human breast cancer cell lines. Apart from the MN081/MT450 couple, all the tumor systems employed consist of clonal cell lines which are derived from a primary tumor and which only differ in their capacity for metastasis. This metastatic potential is indicated.

Each lane in the northern blots was loaded with in each case 2 jug of poly-A' RNA. The blots were hybridized with various differentially expressed cDNAs which were isolated in the MLSSH and PLSSH subtraction libraries (screens). The hybridization probes which were used were selected randomly from the metastasis-specific genes which were isolated in the MLSSH and PLSSH screen. In each case, they represent 10% of the 20 Sisolated genes. A rough classification (correlated CI index) is intended to describe the correlation between the expression of the genes and the metastatic potential of the cell lines being investigated. Genes whose expression is upregulated in all the metastatic cell lines and is not present, or is significantly 0 reduced, in all the nonmetastatic cells were indicated Sby Genes which are clearly expressed O differentially, but not exclusively, in metastatic 10 cells were indicated by or depending on the strength with which expression was correlated with the metastatic potential. Expression some clones exhibited a strong association with metastatic potential in only one tumor progression model.

Fig. E: In-situ hybridization. Sections (6 Am) of formaldehydefixed and paraffin-embedded human carcinomas were hybridized with 35S-UTP or fluorescence-labeled sense and antisense RNA and subsequently counterstained with haematoxylin and eosin (H and The carcinomas were graded in accordance with the UICC guidelines. The scales represent 100 pm b, e and 40 pm (c and d) and 20 pm (g and h).

a-b sense control; b, radioactively labeled antisense CD24 probe): CD24 expression is a moderately differentiated adenocarcinoma of the intestine, graded as pT3C; p21; pNO; pMl. The section shows significant overexpression of CD24 in intraductal carcinoma cells (located in the cytoplasm) whereas the nonneoplastic mucosa is only weakly positive (constant basal expression).

c-d sense control; d, radioactively labeled antisense CD24 probe): CD24 expression in a moderately invasive ductal, moderately differentiated breast carcinoma, graded as pT2; pNlbii. It was possible to detect a positive signal in the carcinoma but not in the surrounding stroma.

21 e-f sense control; f, radioactively labeled antisense S7 probe): S7 expression in a moderately Z differentiated adenocarcinoma of the intestine, graded as pT3C; p21; pNO; pMi. The section shows significant overexpression of S7 (predominantly located in the nucleus) in the carcinoma, but only very weak 0 expression in the nonneoplastic mucosa.

h-g sense control; g, fluorescence-labeled Santisense S7 probe): expression of S7 in an invasive ductal breast carcinoma which is not differentiated to Sany extent and which is graded PT-1C; G3, N-1B1 or I, R-O, L-1. While it was possible to detect a strong nuclear signal in the intraductal carcinoma, hardly any signal was observed in the stroma.

Claims (14)

1. A method for identifying metastasizing tumor cells, characterized in that at least one cDNA sequence which is selected from a population in accordance with Fig. A and/or B, or complete gene sequences which are derived therefrom, or functional gene fragments thereof, or their homologs or alleles, is/are used for hybridizing with tumor tissue.

2. The method as claimed in claim -l-,--eharacterized in that the cDNA sequences which are selected from a population in accordance with Fig. B are involved in the metastasis of pancreas tumor tissue and/or the cDNA sequences which are selected from a population in accordance with Fig. A are involved in the metastasis of breast tumor tissue.

3. The method as claimed in claim 1 or 2, characterized in that the cDNA sequences in accordance with Fig. C are involved in the metastasis of human breast tumor tissue and/or colon tumor tissue.

4. A method for identifying compounds for treating tumors, characterized in that a) a metastasis-specific gene sequence which is derived from at least one of the cDNA sequences which are selected from a population in accordance with Fig. A and/or B is expressed in nonhuman mammalian cells, b) chemically, biologically and/or pharmaceutic- ally active compounds are incubated with the abovementioned cells, c) those compounds which exhibit a modulating effect on the expression of the genes associated with the tumor metastasis, or on the 23 activity of the proteins which are encoded by i the genes, are selected. A measuring system for identifying compounds for treating a tumor, which comprises at least one gene, which is associated with the tumor \O metastasis and which is obtained from a cDNA IN sequence in accordance with Fig. A and/or B, and also at least one chemically, biologically and/or pharmaceutically active compound.

6. A measuring system as claimed in claim 5, which comprises at least one protein, which is associated with the tumor metastasis and which is encoded by a gene which is obtained from a cDNA sequence in accordance with Fig. A and/or B, and also at least one chemically, biologically and/or pharmaceutically active compound.

7. A compound which is identified by a method as claimed in claim 4 or using a measuring system as claimed in claim 5 or 6.

8. A cDNA sequence which is selected from a population in accordance with Fig. A and/or B, or a complete gene sequence which is derived therefrom, or a functional gene fragment, or its homolog of allele, for use in a method as claimed in one of claims 1 to 4 or in a measuring system as claimed in claim 5 or 6.

9. A gene product which is prepared using at least one cDNA sequence as claimed in claim 8.

10. A genetically altered nonhuman mammalian cell which contains at least one cDNA sequence as claimed in claim 8 or at least one gene product as claimed in claim 9. 24 (C 11. An antibody for specifically binding to a gene product as claimed in claim 9, which is prepared using at least one cDNA sequence as claimed in claim 8 or one gene product as claimed in claim 9.

12. A probe for specifically hybridizing with tumor tissue, characterized in that it is prepared from O at least one cDNA sequence as claimed in claim 8, it contains a label which is suitable for detection purposes, and/or it is 30 nucleotides, C preferably

15-20 nucleot-ides-- particularly preferably 10 nucleotides, in length. 13. A test kit which comprises at least one cDNA sequence as claimed in claim 8, an instruction for preparing a probe as claimed in claim 12 and instructions for hybridizing and detecting nucleotide sequences in tumor tissue. 14. The use of compounds as claimed in claim 7 for producing compositions for treating cancer diseases. 15. The use of antibodies as claimed in claim 11 for producing compositions for treating cancer diseases. 4- 1/115 Forschunaszentrun Karlsruhe <120> Method for identifying metastasizing tumor cells <130> KFK-9903-PCT <140> <141> <160> 289 <270> Patentin Ver. 2.1. <210> <211> <212> <213> <220> <223> Clone #2 (MLSSH) <400> 1 accaggagct gatgaacgtg aaactagcgc ttgacatcga gaicgccacc taccgcaagc tgcctggaggg cgaggagagc aagctggagt ctgggatgca gaacatcagc atccacacga gaccaccagt qgctacgcag gaggactgag :-tcatcczac gggggactca ctagccc <210> 2 <211> 533 <212> DNA <213> Rat <22 0> <223> Clone 44 (MLSSH) <400> 2 azaggcttgt aagtgcccga agtgtaagcc caactacaga gatqgtctca= aatgagtctg t-agactacag agctactttt ccagaagacc agt-tcccaa ctcccctcag aatggagcct 120 gcagacaagt gcagtatcct ctaacagatc tgtcccccat cctgacgagt ggagactctg 180 2/115 at atat ccag acczactcca atgaagtcat acggaaaaaa tctcccagzt cactcttggg ccc at tacta agcggtgcag aggaagaggg aattcaczat tctgactgag aatctgcctg caaaacactg cacgcactdt cat :czgcct qctgtgaaat ggaatcatca cagagttaag Ztcacata ctggacccag gtatctatca ccttgaacag tgaaagacr ggtcccczct cctcagcgct tagcctgatt tgggactt-tg aa'cacaqat cagccacccc gg:tgttrctg ctaaatccaa gtgcatt1tca ttggacaqtg atagaagaac aatgttctc ccc <210> 3 <211'> 62.3 DNA <213> Rat <220> <223> Clone 45 (MLSSH) 40 0> 3 acagagatat taccgattg cacc gagagg gaattgtggc ggcacagtgc tgtgaacccc ggaaactt tg aaaaaatgga tgcat -tacz atctttcccaa tcattctaaa atttgtgcga aagaacagct ggtccctcgg ccccttcttc ggcacaatt t aggc cacgga aggcccggcc aaaaacaatt ttatcataat ctcagaagaa agc cagaacaccta ggagtcttcc cacaagatgac attgcagczc gcggaaactc tggttcattc tgagggaagt tctctcctga aggacqcaga ttggattgaa gggaaaaaaa aatttttaat actggctttt caggaagaga cctggtggcc ggttccatct acaggacttg aggttcaatg catgagagca aaaaccttct ttggttttcc cagtaaaagg gaacgtgtaa attctggtcg ggcagaagga gaactgatgg gttcactccc actggcctct tgttctaaaa tttaaaaagt tatvttttt ca agtgcgtatg ttgtgcaaag ctatccaaag tccaccggt t aggctcatca aaaatagtat ctcaaagaaa tggctat:t tactattc--g <210> 4 <21.1> 335 <212> DNA <213> Rat <220>- <223'> Clone #6 (rEaSSH) <400> 4 acagatggca ttgt-tcatga cgcaczccac caccatcttc ccgtccttca gtctccctcgt ta:cqtgctt tctttccctt cccactcctg gtgctggacc agggcaccgt ctgttaaggz 120 gcagaccgtc tcatttttcc tgccatcagc tgtggtttca tcaaacttct ctcccaaggt 180 3/115 gcaagaaaac acggtcktct tcaccgtgcz ctcagttttk accgtgaggt tgttaccgtc 240 tagggtaazg atgcagtctg gtttggccat tkgcacccat czccctaaga gccaccccta 300 ctcctacttc cttcatgtag ttctcaaacc cgtcrg <210> <211> 582 <212> DNA <213> Rat <220> <223> Clone 47 (MLSSH) <400> aCtaatcatt tgractaccca ctggacztc ggacagcaag gcgccttcat tctttttgcc actttaacaa gttattgaaa gt aagattgt agcaaatgtt ttcaggggac atcttccaca tccacactga agagccctgc tttatggtta tcaattatca tgtaatatat caggatgcgt aaatacagat tgcaagcagg agagaaagc t agcacctgag aactgtgggc cgtctcggtg gaaaggcaca tggagttt-tc ttatttttcc gggactctct tazttattaa tagctqaggt :gctgqctttc tgagcagggg g tc t tc t goa agctctagct aaatttttat caactctctt ccctattctg gaatcatctt ccctgttcta tg~tcagcaaa ctcatgctgc agggagggaa tgtataacat gcctccgcag caaccrcgaaa ctogtttttg gaggattcgt catagtgagt cctagaatca tc ccctgagagc at-cctgctc g cgt-gzctaa gaggggcagt cattcctttt tttaacaaac ctgaaggatt ctttatgact aactgcatag <210> 6 <211> 289 '212> DNA <213> Rat <220C> <223> Clone #8 (MLSSH) <400> 6 acaataagct aacagaaata gcatacact t-ggacattga tccsaggctt tcccaggaga cgtgtcaaca tttzggtga agaacttgaa agacttczta tgaagggcat tggtatcctg agaagccata caaaggctca gggtttagat 120 aggggagaag gtggacccgg tgatcgagca agcgtccaaa cagagtggtc 180 cgatgtzcgt ggcaatctgc cggcaggatc tgagcgtctg gatcgacccg 240 cctaccaaat cagtgacaag ggaccagtga aggcgctg-t 289 4/115 <210>' 7 *<2171> 574 *<212> DNA *<213 >Rat <220> <223> Clone #9 (MLSSH) <400> 7 cggccgccag a:ttEaccta gtgaztaccq cgaactgtca acttctacaa agatzgacaa caatgaccac t:tgtagtga gcatgtttaa cctcgaacatc tgtgatggaz tgacccatg aggctttggt ctgcagcagt aagaagaggt agaatacttg ctccattgtg aataatagag aattcggtct ttttgatgaa atctgcagaa att ggc aact ataggatcac atgcacttct gcttcgcatc ctaaaaatgg ctt.tagaata tgagcatcca gtttaaaatg gaacaaggtg ttcggcttag tactatatct aaatttccaa tggtagcaca tgtccagtga cagcagagga aattctcaac ttccaaagct gcagtcatgt gtat cgtqgtgcog ccgaggtact tgaacacttc tttcrtgatga gaatctaagc cagigttgcta gcggaatgaa ccatctatca agagggaz~ggE agactattca gtgaggtgtg ccagtataa ttcccttgct ttczatctcg ttactaccag tggcgttgtt atgtggtttg caggcagaat <210> 8 <211> 565 DNA <21-3> Rat <220> <223> Clone #10 (MLaSSHi) <400> 8 actctcagaa aggc tgagac at.gacttaga tcc::gataaa cacttcctgt agccctcagt caaaagtggg acagc ccat c agaagacaag ccagg-gctgag aggtaagatc gcagtcgtcc ctgactttcc tcttggggcg tctgggctgc tctctggcaa ttccaagtgt tatgaagagg tttgcagaga tttaatattt aacccgaag tctggggttc acttagctgc ttttcaczga tatctcctaa gacccccgaa agatcaaggt gatcagtaac taaatt cagt cttccaccg tcacctgtca c acacagctt gcgaagtaat ttgtca gaac gaagggcttg tc:ctctgac caaattggcag cctatggttg gacacgcctg gga tgaaac t ccgtctaact tatagaagaa agtggagat t attccagtca aagc tgaag aaaagcattg actataactc tctcztgtca ci tgaacccg tcttgcaatt tgzgactctg tgttt:agac ttcaitggca aaatattcta tattttgaag ggttg 5/115 <210> 9 <211> 381 <212> DNA <~213> Rat <220> <223> Clone #11 (MLSSH) <400> 9 accaaczcct cagttccaac tggggtggc c gaaggaagag cccgttztcc agcgctgcgc tgt gaacaac tccatatccc tgcactggtt. ctactttttg aaatctacag tgaccaggct tttacccagc t cc acgac at act tgactgg tgcagcttcg gatgcggcca gctgagagag agaagattac atctgtgcag actggctccg ggaaacagte cagcaattcc gcccggagag ccaccaggtg gaatctggtc cccccatcct tactgttgta ccctgacggt tccacggcaa gacaatagaz gcctgacttc ccagcatccg aatactccgc gaccaggaca acctcctctt zcatcctctg ct tatgagac <21.0> <211> 599 <212> DNA <213> Rat <220> <223> Clone #12 (MLSSH) <400> actaccttat cactgtctgg tttqgtat-aa aatctgttca acctcaggat taggacagtc ccgagtgtga ccaaatcaca ttzaaacctt cacaccatca aaggaagcac gctggccagt aactgaaaaa gataaaigtc gatgtgcagg ctcttcaagt tggttcaccg cacgttttaa gtgaaccatg acattgctgt ttagtagact ttctcatgca tggaaaaaac agcagccagt aaacgggtga gccccaatcc ctgtgcacac taagaaatgt actcggagcc tcaggaaat: cct-tcaagtt tgcagcttgg aaattcaaac ttaccgcaaa aggctaaact catggtgaca tgcattggag ttactaagg agcagagtag ataatttacg ccacttgcta tgattgagca tctcagjatgg caaacattta ttgagacaca gtgacaccct tgaagtgaac agcatctttg gctgrtgtctg tccattccaa atgattaaca cagtcaggcc cttctagttc aaattggttt gccctagatg ggtggcgagc aaggctgtca gactctctgt tggacttgag gttgtaaat. <210> 11 <211> 569 212 DNA 6/115 <213> Rat <220> <223> Clone #13 (MLaSSH) <400> 11 gccgcccggg ggcgact tc aacccaaagg ttzttaaaaa caacaggttc tctaaactaa tacttaacga aaaaagaata gtcgcagatc cactqcctta caggtacaac tgattctgat tggcagttat aaaaacctgg cccgaagcgg caatttcgtc cacttgctag tctaatatgt acqatgtaaa aaatgacact gtaatgttca tgctatcagt gagattagga agagtcagga qtcacaaaca ttccctgaaa aaaattacat cagagaaact. tcactgtaat tattccttc tttcaattgt aatgccccaa catggatcct gcaccaz-aac catacggcaa aaagacatac tctgtcttta tggaaacaaa taaaattggt ttatatggat ag-ccgagca acttctcttgt gaagatctca gcccaatcag aagctgctttt atatgata czcatgtgc caccacatgt gaatgatact acagagtttg tataacactt aaaaaaaiaa ggaaaatgta tccacagctcg catccccata qttaaatccc ttgggttac <22.0> 12 <211> 399 <222> DNA <213> Rat <220> <223> Clone #14 (MLSSH) <400> 12 acctccct-ca cccccttgtt Laactttaga aagggaggcc cagcat--taa gcacacigttg gctctgoo ggactaggcc taaactgtga acccattaat cacggaggct ggtcggaatg cctcatc ctc acttgccctg tcatgtctcc atgtatccta acaggcatag tctggagttt tttgcccggg tccctcatct gagcaatacc tgtcctcaga aagcatagc aactgggcct catgggaggc atatgctg ttgcttaaca zaatgaaca ggaagagaaa acacca gcac tctt--ggga ctgcggggga agc-tgaacc qccaggcaat caatgtgaga ggggtctaac gcttggggg cttcaaatgg tgataactaa gcattagact <210> 211 <212> <213> <22C> 7/115 <223> Clone -415 (MLSSH) <400> 13 acaaco"ttCt ggccaaacta gaaactaagt caagaatca-. ctattttctt c tgt c act tt caatcactac atgagtgta gaacaaatag gtgztcaata gactacttga gctcaggcca ccacagrttta tttgtaattt ttcat-acag tactgzgtaa ttctttgctc actatgtttc acacagggag aatgtgtgtt tactaatt-at atacatttga. aact ttaaag cat-at ttcct gtttagaaga ttattgccac tagcagtcta taatgtaaat cccgtaaagg cttttgtqtg gctgaaatgc acgttaagac gtttatggac tcaaacct-,g -ttgtttta cqaagt tgaa. cztaazgaat ggaattgtgt gaccaaaatc tgaaga-gag caaagtgc atggcagcca caczggagaa aaacttggaa gctI agggca ataacactca cttttctata gtg~gtgggga tagtatctgt agaaatgc-.c gctcacctcc act gtgtgtg tgtt Igtaga ttccaagtc aaaacttgaa. aatctttgtgg aggt taaaaa. cgtttacagc aaoIt tttt tcacaataa caagggtgaa cctactgtcc gaagagactg gagcacttat <210> 14 <211> 554 <212> DNA <213> Rat <220> <223> Clone 416 (M~LSSH) <400> 14 actgggaaag actctgcagg gtccctgggc agttagctgg I tgg-.gggac aacaaottta tttcaatgac acttgtc-at aaagccgata aaaaaaaaaa ttggtta-ct agcaaaagt tagtttaag tcaacttgaa tagcatgtca gatttaatc tcctlccact ctgtgtccta gagtcttgtt aaaa tgggggttca tggacaggta gggacgtga cattgttaca c-taaagcggg aagtt.cgtag tggctcttag gtglcctctt ttatttttct actlcattac gccagtggga. tacctaatcc ggcgggtggg ccl ttgata ggtttctaac gggaactgag cc::ccaggcag tttataataa tacttIagggt tgccactgct acacacgagt tgttagtggg tattaaatt'- tttacagaat gacaagcctg actgtcccct acacacccca r.ccctgccc tgccgccact tagaaglatg gggttattt I t-aaagcaa Igcclgtttg gagttaatac tccttctgaa cctccaaaaa <210> <21.1> <212> <213> 8/115 <220> <223> Clone #17 (fLSSH-) <400> acatagatca cagcaggcag atccagacta ttcgaatggc tcattttgtc ttatrctgga gcaccagctg racgctn.ttg acaaagacag cagcaggaca ztcagccaga ctcttgtgga ~aagctggc agactaactt ccagtgatca tgagaacttg tggc tgaaca atcattgaaa atggtat tgg ccagagaaga atctgcagca tcctagaatt gaggaggctt aataggacac tgtcgatcac tgacaacaac ttccazgggt tgaca gctgagtcct cc"-ccccctt. ggattcccca ctgaattttg tacttcaaag agaatagcat ,aa--gctaaaa c aatat .cca ttgz gggt tc gaacagzgtt gcagcattat aaactttgtg INO <210> 16 <211> 384 <212> DNA <213> Rat <220> <223> Clone #18 (?MLSSH) <400> 16 ggtcacacac ttztccttct- tcgtataugt, tgaaatacct atttagactz aaaaaaaaaa ggccatttat tagaaggaaa aaaatggaca tatatgcaaa taagctgtta cttatgtctg aaaaaaaagc gtaaagtcct caatggtatt gctgactaca ttacttcaag agtgtaagtga catttgttac t tgt atttccztttt taacaagtt~t agacaccatg agttagatca cagagtagga tgtqctaata t taaaaaagt acaaagatga taggaaacca ggctttgtgg actgctcagt aaccatatta tggaatttgt gtttgttacc ctagttaatg aaagctgtag cgattggttg agatcaaaaa <210> 17 4211> 114 <212> DNA <213> Rat <220> <223> Clone #19 (MLSSH)- <400> 17 catgctcgag cggccgccag tatgatggat atctgcagaa ttccagcaca ctggcggccg ttactag~gg atccgagctc ggtaccaagc ttggcgtaat catggtcata gctg 114 9/115 <210> 18 <211> 553 <212> CNA <213> Rat <220> <223> Clone #20 Cf'-SSH) <400> 18 aagcattcgg gaggtctcct aacactactg acaaaagg~aa tcaaggaaat accaatg-tca cgazccatg aagactttgt attcgcctgt tcatgaaaag gaagaggcaa tgttcccggg tgaccgtatt tggggaaaaa aactatctaa tttcgttttt gaactctgtg agaatttcaa ccc ~gggagtqt taggttccta agatcccaga aaaaacttac aaatatgaac ctctttaaaa agagcztcca gactcataat cat.cacaca aagacggaga atgggcaagc aatgtctgtgz tgtagaacca tgaaccaaag aaaaaaaaag atcctcacat t~ttggcCtg cacactacct aaaaaatgat a-tcagtgtgt ttttagaagg aaccccctct tattccaaac tatttacaga cccaaatgct ctaaagacca tcgggtctgt tctggttatc gaccacgcga tatgtgtagta caggcacagg gtggttattc aattgtataa agggttgcat cgttt-ttaaa <210> 19 <211> 512 <212> DNA <213> Rat <220> <223> Clone #21 (MLSSI4) 19 ac-tg'gagca c t taggccag aagtcaacg tcggtctgca caczat.ggggc ggataacaat acacagtgag ttccc .tttac aaggctatcc atacctcatc tgccggtcac gaagtggcaa ttccacagga ggttctgagg gggcctgttg ctacgagcag cgagt.cccag ctatctca ca accatagcca acacgtgagg ccaagaaaga agcatggaga agrtgcggcc. ccacccaaqa ctaaggagaa ccccagcagg.gtttgggctg tccccacctg tcccacccct gcagtagcgt ctaccgggca ctcagcatci tcaagcacaa atcaagcaac tg actccttggc ggcctgtggg cctggcttgt gcagtagaaa ttggcaaggc caactcacac gatggacccc actggacaag gtgzcccatg aagactggca ccttgtagtc gctacggctg catggtctgt cactgtttgg gtgaatgaaa acctacccaC 10/115 <210> <211> 556 <212> DNA Rat <220> <223> Clone 422 (WLSS-) INO <400> tgctagaatt ttaccaaagg ccacgaggct agcctcttag cgc aaaatgt cgttccctgct ttcaactcct acatcagaca tgtztgtccc tcttccaaga cggc tt t c cttcagcact ccacaggat c agragcaagag gttcctggtgT gaccctcagt tcatgatctg cctggcggaz caagacgttt attggt accgqccgcc cttggtccag cacaatcatt ggctgtattg cttctggatt caccttctgg cagaatggcc cgagcttcga caccagtgaa gggcaggtac 9cattgagat ttgagggccc tta Ecactct ttggtcatgg gcatcattga atcttcacat acctccttgg gccaagagte. caggacgctc agccacaatc cccactgaaa ctrccatctca gatgcagctg gaaataaatc ccaaagccca agaggcaaag tccagtgctg acgctccaga ccgaactr7--ccccgtt t a caacctgcac tcgcttctgc tgtttttctg cagtgtggca tacgttggtt ccttactgca <210> 21 <211>' 530 DNA <213> Rat <223> Clone #23 (MLSSH) <400> 21 gcaggtacaa ttggcttgaa ggaaggttct cgaagagitag gatcattaca Z gtggtataa gtattgagga tctgtartcat acagcgaata gcttt-ttttt accagt--ata tcgaatgrzgt qaaattgaga aggacggccg gcatetggat aaaaatgtta t tagggtata ctgctcctat gggggttca ggtaaggtog gcacttctcg taagtgagat aatcagagta tgtttacacc gcctaagaat agataagaca tttttttgag atccttcc.t ggggcatcca tt-tgatgcg gaatgagcc t acgacgaggt tacaaatata agtgggaatc tagtggaatg aagacataat tcttatttaa tgcactcatt aaggcttctc atagaggaga atccctgcta atggcaaagt agtagacgaa agctactacg ggttatgaaa cttttacata ctaggttagt aaatcatgaa ctgtatttca atcctaggaa gggcttttgc gccagctatg 11/ 115 <210> 22 11> 869 <212> DNA <213> Ra t <220> <222-> Clone #24 (MLSSH) <400> 22 caact,:gact taatgcatca caztctccgc cactaattat tcctgttta act caa tagg catga-ccaa tatacggagt taattttagc ttctacqaccc taattataac catcagtaag zcatoccgagc tagcaaacac aaataatctt. cctcccacta aaaactttac aacaqaacta cattacacga tacactaatt aacactcaac ca cc at c a ccatctatga agcaattctc cctaacaaaa tagctcaatc ccatatagcc tacaatacta caac tacgaa tc cat taata ataatgctcg ccagccaaaa zcacataaaa aaagaaaata atctcaatac attttatttt tgaggcaacc ggctccatcc ttcctaatcc zoactaccat. ttaccaaaag ctaaagctag tctt--agcct tgcctacgcc ctagtcatca ataatcgccc agaattcaca gcaacatga ttatltagcct atatcctgtt aaacaaaaca cactcttaat tttccczcac gtataatagc cccacgtaga ggggttatgg acccattcac aaacagatct cagccattat acggcttaac ccaaatttta c gaagccact. cttaaatgca tgccctcatt aacacacccc atttataatc agctccaatt gataataca catcctccca aaaatcatta aatccagaca ctcaltcactc ctcatcataa c:taatcccaa agaatttatt tcaatccaaa ctaccctcaa aaaataccat, gCaggcta gtttccatca ttatgaggca attgcttact ccatgaagct ttattctgcc gccgaactat aattatagct. coaggat:ac 840 869 <210> 23 <211*> 435 <212> DNA <213> Rat <220> <223> Clone #25 (MLSSH) <400> 23 acttcctcat tccctcaagt gtcctacgat ccactcctga cccctgtgac aaccatgtgg gctacctttt tgagcgtaga ataagccacg gagaatgccg gtctagacgc gacatcacCa acctagaato ctatgttgrta aagaacartgt gctgcacagg ccctqgagaa ctaaagacag gccatacgct tzc!tCttttc tattcaataa gtggcctagc caactacttg agttgttcag taaggaagaa ttgtttgaat agctctctcc atgcagtgaa tgcctgtgcc gcagacaaag aaatccaccc cttgaccagc atggttttta atatagggaa cgcctgcctg tcctacccca ggaggaaczg agaggccctc aacaagcccg aatgacccaa agctccgaz-g ggc tgggcct 12 /115 aaaaaaaaaa aaaaa <210> 24 <211> 689 <2,12 DNA <213> Rat <220> <223> Clone 426 OM~L.SSH) <400> 24 actttggtg aaagggcggt aatggagaag gaaggagcag tcgcggaaka tcaaaatagc gaagcagtat cagttcaaac tgraagzttaa gctatgcttc taataaatcc ttttagtgag g-ttgaatcca tagaactgcc tatggacaac aagaccaata g-gggt tctgt aaataccaca tatcagcagc ggcggtgatc tacaaaccat tttccaattt taaatttttt ttctgagttc agtatcaatt acaagcccag ytttgtataa ttcattacct atgaggtgt agcagcagtg actaaattat gaagattcat ctatcaagtt tcattaaaag tgtgttttat tgtgacagtg aaaaaaaaa ttaagggaag tagtaaatgt gggatctaga ttatgggaaa tccatttgca ttgaaggtcg cccgaatgga aattzacttt gcccccctcc tcatgatgta agggaaccag tgaagaagat 120 gaaataaaag tagccatgtc 180 ggagggt ttg gtatccagac acttatcccc ctcctgccac agtatgacgt cattatttta cccccagtat atagt-gtctt caggaagagc gaggtqgtca aacaggtggt ctgcctaataa tgggt ccci c tttcttaatt tgtagagcaa accggttttt <210> <211> 691 <212> DNA <213> Rat <220> <223> Clone 427 (rMSsM) <400> cztctcacaa cgt-tcttgcc gctgraggaca aagttcttcc ccqgttcata acagaagttc cccggcgbac gaactgaaca ggckagacca ttgcggcagc agacatcggg gacaacaacc cagagtgacg aacgacggag ataaaggcgg ccgtgcggga ccgcaagaa OctCt cc aag agagtagata ccagagaact acaggaacgat tgac tgcaga O aga aaa tga tgccaagacc atgtctgcca cc tggatagga gactgagtca tggggcggat akaatcctgg- gcatcacgga cagacaccit gccaagtgaa gatgagctca gagacaaagt gaattccagg catcctgagc tgaaccacaa gggatatctt agtatttccc ccttgatcoa aaatggtgca ztc::aaggc ccaagtctac ggaagacaga tcaaaagccc tgggactggg aagctcccaa gaagcccttc tgcaccatgt tccttgtt~a gcctgataa octctgtaag cacccccccc aat.aaaatca ttzctcatca aaaaaaaaaa .3/115 qaggggaagg ggcaaatctg cctgaaoctt 480 cctctcccga actacttiac cgagtccccc 540 gggaatgcaa tagtcttgtaa tagtgggtag 600 tczggcagac aatgccttta aaaaccaccc 660 a 691 <210> 26 <211> 390 <212> DNA <213> Rat <220> <223> Clone #28 (MLUSSH) <400> 26 acctcttgag ggtcattt aagatacagt gatacaatgc acgatttctg at~ttcttttg aaaaaaaaaa ccttgaactt-tgacctctgc ttaagaaaaa gaatgcacag .actctagtt tgattaaatt tgtgccctaa aatatatttt tttagataat acaccactac tggztattaa aaatctcaaa aaaaaaaaaa aaaagcttgt agcaataaag agztgttaca cttgcaaagt ttcactaata attctgttaa tttctaaatc cagcatttct ttttt-aagtg atcccttctg gtttattatg taatcattag tacaagaata acacatataa ctgcatttaa taaaatttgt gcacatcagc gtgtgaaagg aaacttttta <210> 27 <211> 603 <212> DNA <213> Rat <220> <223> Clone #29 (NrLSSE-) <400> 27 acatc-ttctt agacaaaatc attatttact act taaggag ccacatcaaa acaaaccaag tcctgcatac gaatccztagt ttcctccacg ccatcccatc tattcatttc gacccaggac ccagaatgat aggggtcgta ctcaaaacaa agccaacctc aaacaggatc catattatac cttaattaac aatttattac att'ttctct gccctaatct cgcagcttaa ctagtcttaa aaataacccc acaggattaa aatttaaaga cctccttagg ccttagttac ttattctttc attccggcta acccccttca ttgcctacgc tattctacgc tatcaatcct aatcttagcc cattccgccc aatcacccaa catgaatcgg aggccaacca actccgacgc ttgttatttt ccaggacctt acaccccacc tccattccca ttcctaccat atcctttact atagaacac 14 /115 catttatcat tattagtcaa ctagcctcca tcagctattz ttcaattatc ctcattctca 540 taccaatctc tggaattgtt gaagacaaaa tgttaaaata aaat-:aacca aaaaaaaaaa 600 aaa 6C3 <210> 28 <211> 354 <212> DNA <213> Rat <220> <223> Clone 430 (M~LSSH) <4CO> 28 accaaccacc tggttgccca ggcccacgtc cctcttgacc gatgggctct taacaagcag ccaagtccta cccgtctctg cgcttgctgc etcgctctgg gggtggttgg attccaaaat aactttctcc cacaccgcac cccttgggtc agee tcggt t cgagctggct acatttgtgoc aggggt tgac atcctccat accagatcct gac aagagga a tgggac ct c tczccactgg tcaagacraaagggaacctc gttccattcc tggaaggaga gcctcttatc tcctgagacc ctgtcgggtc tggagagata tgctggcttg ctacccaagt aaaaaaaaaa aaaa <210O> 29 <211> 624 <212> DNA <213> Rat <220> <223> Clone 431 (.MLSS-i) <400> 29 at aag cttt t tctttcacaac cacgccagaa aacttttatg -gggaagacc gcgcttttgc age aatgaag tzggattttc accaccaccg tgaaactctg aaagtt tcga agccggctgc aaatcctcaa ttatlt-tttcg actacqtgtt tggaaagatt acttcgattt tttttttttt ggaattcaaa ccttatgctc catccagttt ggatggcgtc tacggctttt tccactgaa teagctgagg ectttgtcgc tattatgaat gctaacatcc cacgttgttc eacacggatc gtgcactgct teCgggttggc Ctttttctcc aactggtaca g~gtgatgttg gacat t ttat ttgeetgtga tgctgtgett etc ttgccca gtcagggtgc ttgggecagaa aactcacaaa aaaattatga aa-t ecgca tcagtcattt gcttcttgta tgtctaaatg caatttcact ggcttctggg tcetcctetg etacccggac tggcttttcg getgcgeett caaazecgag ttcateteca getcgagcag cgcttctcg ccattgggct teat ecetgagag atgecagact cgaactcgtc 15/115 <210> <211> 435 <212> LDNA <213 Rat <220> <223> Clone 432 (W-SSH) <400> acctcatcac tgtctcacgg gtcaggcatc ggggtcttcc aggtctggac aac ggaga ca tcagaatttg ccaattcctct cactcacqcc caaacactct tacrgatatgc tgacatttgg gg tgct ctt c gtqaagaaca agttccaaga tgagt acctagtatt tctcttcctc tctgacaaca at!ttttccat caggaaaggc gtgcagctat cttggatgaa tgggttttga atttttttct aaatagatgg ttgtgaaaaa tcaaacttgc gtcttacaga aagcaaaatt t gagcag ct~g caaagacgaa tttttgggca tzaggtgr-tg ttagatcact g tg tcgg ccc cgtctCtctg tgactccatg tc tgggga gagacttcca cgtatgttaa aga tgtgagc cagtcccttc gttat-agccc <210> 31 <211> 46B <212> DNA <213> Rat <220> <223> Clone #33 (MSSH) <400> 31 actcttagcc gatgtzgatg gaaagctaca ggcattggtc tucagaattc gtggcacagc agaaca tgat ctctccaggt agactgt9'Lc ggtcacgtgt ttaacacctc ttcccttcat ctgtggcttg acagaazac t ctgc tcaaqc tcagct:ttat taactgctgc tccaggcttt agcatccaga gatatccaac gggaaatggc gaatcttcct ctcacctqgc gaagatc ttg actctcagaa gcaatattta attcaagaac acac ccc taa acttcttcgg aicagcttga cctcttgtca ctaagccgcg gaaactgaaa cgtaaactct actactgaaa gctctcagcc agagcggcac aaagcatgct ctttact tgccaagtgt aaccaaagct qcaaccatcc aagctggcag ctgaaacaat agagtctgtt cgatataggt <210> 32 <211> 196 16/115 <2:12> DNA <213> Rat <220> <223> Clone #34 (MLSSH) <400> 32 accaggacgc aaggcggaag ctttgttttc ggtaaaca~gt caccgcagaa ctgtgcttca tttctgctgc c z tgg gaggaagagg atttcgcaga agaggcagaa gaagaggcct. cctcaggctg ctagttccc ttagcttttt tccaactgcc 120 ctctgtcctg tttcgttcc gtttggtttc tccatggg 180 196 <210> 33 <211> 435 <212> DNA <213> Rat <220> <223> Clone 435(MS) <400> 33 acagacagtg tgccccatat atccaclttca taaaggccct agcccatggg ggggatgaag acctcaagct. agaggactta tctgaaggaa agtatatgtc gtaagtttga gaacaatgac ctgttctcct cagrgtcttag gqccaggtag tgagt gcacttaaag cacccaagaa gagaatcttg attcccaccc ttccctggga acaccaagg gctgggccca tataacaata aaggataccca gagagtarctc aacaccccca ggaagatttg atcaggccaa acatatgcct. aataaaacct ggtcctgggc aagtcaccaa gcacagtcct ttgggcccac nnttggtaac gtcatt-cagg accataccec tgtaaggact gtgaaactgt cacttcctgc gctttgctt.t. ttctccatg qqcaaaacga <210> 34 <211> 758 212> DNA <213> Rat <220> <223> Clone #36 (KLSSH) <400> 34 ataccacact gaggractcac tcttcggaga accr-actgag ttcgraatatt tgcgaaaaat 17/115 gctgzttqaa cctaagattc gtcatggctc gaagaagctg tcgtgtagct t tcttggtgg tctctgtggz: tgggttcztc tttctt-ctta zaaattagag ccagatggca tatatgatgg cctgatgartt cgaacctcat ccctcccaca tgaagacaca ggaaatggtg tcaaaggctg tccctctctt aagacttgtg aatttaattg gcacctcatg gzcgagagac aagctcagaa cttgaagaaa tgtggtgttt tgztaccctg atagttttgt ttctgaccgg taaagaacta caatacattt aatatttgct tttacctagc caaccatg aatt ttggaa tggggagac t gcggagaatg gccacagata tctttttcat ccacccgact tcttcct tat tgaggtqaaa aaggcttgct ttttgtacct gccaaagtta agagaagacg gaggctgggc gcgctqtcat catagctttt tcagtttttt tggctgttca ttatttagg cttagtgaat tcttcaagct cagcgcgacc taactactat ctcggctgat 0 .tccgctgct catggagccat gaagcagaca tctgggaagt gtgtctttcz gtggtttctt ttttttctga atgataagtc acgctaacicc gaattctgca gatatccatc acactggcgg ccgctcga <210> <211> 209 <212> ONP. <213> Rat <220> <223> Clone #37 (MLSSH) <400> acaggcacag ttcaccataa agaggatztga tgaaggagat agatttccac tctccactcg cctgggtgct ggtgcggtcg gccgttggcc accgactgct tcttaaactg accct:tggcc gczgtgggag aatttctcaa tgactgactc gatccagatc gagacggtag gacatgagtt cgaagtccca tccaggggta ttgtcgaac <210> 36 <211> 268 <212> DNA <213> Rat <220> <2231> Clone #38 (MLSSH) <400> 36 caagctttt aaaattcata caaaatacaa gctatcaaca ttttttt-ttt tttttttttt ttttttaaca gtttaacaaa actcttz-aat aaaatgcatc ttagagaaca gttccgattg cttgcctttt ccactzccca 120 aattatyagc acccacacac atatacactc aaactacata caaagggcac 180 ttaaacaat:t aaactacaga gaaaccaaca gttctcacag ttgatgcagt 240 18/115 chtcatttgc tcccaaaatz atgtgaat <2:10> 37 <211,> 390 <212> DNA <213> Rat <220>, <223> Clone 139 (MLSSR) INO <400> 37 acaagctttt aactttattg gtgaattagt caagataaaa tgaaaacaaa caaaattggc ttacaaggtq catccgctca gtggctttca aacggaaccc tttttatttt aagatgcaca tcactgtcac tgcaacacgt cttggctaaa agctgaaagg tgttgctgct gtcagtttgg attcccagga ccac taaact tttttttttt aacaaaatca ttacggggag ttcaggacaa tatcaatcaa gttcctttgc atgctacaaa tcacaaactt ctttatcagc gattctgagc ticttttgtt atqcaaagga ggaacaccaa gtagtgaaat cattgatgat catataaaca gccaccaagt tccaaccttg acacacttga aggctcgttt tct-ttccagc attaacataa. caaaagggag cctacttcgg a aadz 6t t c -atg tgggca g acaztcattc aactcaaacc acagtatgat attcatcatt aagtggagat aaagaatagt tatzcctggc Lctttgggaa actctcacct ggaaatcatg aattctttta aaaagaaaaa tctccccatt <210> 38 <211,> 295 <212> DNA <213> Rat- <220> <223> Clone #40 (MLSSH) <400> 38 taaattcttg tcagaatgtc ttaatcgatc attLTgtttta atattctttt ctaaag-aaca ctcttttaaa gagaaactag tatttgctaa gcattagtaa tctcg-catc ttccttgatg 120 actgtaatgc ttccaaaaca aatgccttca gccgtaggaa tggcacagct tgtgaaccag 180 aggccaggac aggtattctg ggttgtgttc cactgatata cacataaata ctttct~ttgt 240 gagaatgtat ggttgattaa acctgtatgt g-:ggtg-tgcaa gccatttztta tagtt 295 <210> 39 <211> 639 19/115 <212> DNA <223> R.at <220> <22-3> Clone 441 kMLSSH) <400> 39 accaagactg tgacctgtat att.tccacca g-tgtztctac acctaataca tgttttaaaa taggtgtgtg attcactztg ztttaaac gaaatgtag cctttccagg cagcaaacaa tttacacagg gcccttgctt tctctgrcatt gcaagtagaa accagaagca c tcat t tga tccctctatg ctagccctga ctgctctggt gcttggggat aacaagttaa aagcagagca aaaactaqtt. atcgtaatct atgattctta gattacaaaa cattttttgg atagaaatac gtttgacctg gacctgagtc caggaagcca acttttgagg gtggttacaa taactccaca gagcagtcca tttataaaaa gttacactta cttatttcta tatattagta agtataaacz tgg-tttccta gaatttacc tcctcattgc gccaatgggg gtccatttcc ccttttacca aaattcttgg ttacattttt. cactttcaaa ttttgtaacc ttagaactta gagatacaag c-tcaaggccc gaaitgqtcga tagcatctct tatcagttgg taatttgtgt aactgtaaca aattgctata aaacgcctcc caatgccaca gctgcagcgc <21C> <211> 214 <212> DNA R~at <220C> <223> Clone 442 (MLSSH) <400> acaaatgczg agtaaagtgt cagccttgra attgtaagtt tattttttta attttggtaa zctcrtaggaa ctaaagttta cactgtcaae ttat-zcvrLnt tgagaaaatg acttttttat attctggctt cctgatcccc aaaccctgga aagggcgcta 120 accagactca ggtcaccaga acagccacat tctctgtggc 120 tactcaggtc aaac 214 <210> <211> <2-2 <220> <223> Clone #43 (MLSSH-) 2(j/ 1ib 41 acagccaatc ccacggcatc caaccttaac gcatcaccca qccctaactc tagaacaaac aaacttttcc ctgaaageca gctaargaccg ctaaacgtca gaaa cacaaa ccatgt-atcc ttaacacaac tcagatctcc tgtcatgctt ggagcactga agaggaa-,cc gaggagacag tttaaagttt ccggaaaggg gacatcttta aagaggaaag aaaatg-ggta cagagtccta caggcttctg taccctagec tccagccaac tcagccccrag agrtcttgggc agagectect aaagaatatc acagccttct ctgaccgtaa aagaaataaa aggaaagaga cctagtcaca cattgctcca aaagctttca caacact-gtc aggctttgct cagcacccac tgagccaggg agaggcc tgg ctacctactg atatccagga acaaaacaac aggcagatgta gagctagtga caaaatctc: aactgacgca ttcctcctaa gag -gcacgg accacccgga atgtttctag gagggataga cagacacragg catttctgcc caccacaaaa gtagagcaaa agaatgaggc tctacaaact cttaagaaca aaccaccaca acycatgctct ccatttgttt aaag tcggce ggtggagaat ttgtatctct tagagicaacra ataccaccec gagctttcag aacagcccag ggaaaagcct taccacaaag cacagcggga ccaaagggag ctaaaaccta ac t ge tcc 779 <210> 42 <21.1> 679 <21-2> DNA <22.3> Rat <220> <223> Clone #44 (MLSSH) <400> 42 ace t agag tagcctgtaa tttctataga ctagtcrtttt tacaazgata catgcagaaa aattttttta tcaagtgcag ttaaggacac gacccaaaaa gztctgttgt atgcagcagt ggagctcaga ttttaaacat aaagaaaaca agttgttttta gaatttctc taacaccaac agttt(-7gtat tcatt..gtgg agagattaga gaactaaaag tggaactgct ttatac tgt aaacctcaag c-tagcagtaa tttaacataa aaatcttcca caatttaaaa attaggaatg caaaacattc ttataatctt zagaagcrtca gagactzttca ccattcacaa atgtcaccat actattgcag tggttgtgaa g-gtttgttctt tcttggttta ctagggagaa atgtgtctgc gtEttgtgtg atttatatca cttggtgtcg acagcrtttgc caacaggtcc ctgtaatgza atgtaaca:c tttttcctt atttaatata. tgaattgcag cccaaaaalt cttccattac aatttacatt gtcagatcat agaggaaaca cagtgaatac ~agaccctg 120 aagcaactaa 180 tttttaaaga 240 ttaatttgtt 300 tttttataac 360 gtaatCaCgt 420 ttaattcctc 480 gtattgaata 540 aaag-tgcagt 600 agccgc-cta 660 679 <210> 43 <211> 218 21/115 <212> DNA <213> Rat <220> <223> Clone #45 (MULSSH) <400> 43 accattcccc tgtgccccgg ctgctzgact aaacg-cttt CCC Cttt CCC gagctgggga tgtattagcc tcaagaataa ttctgaattg agccaaaatt agacatcaga aaqccgcctg gggggcgggg gctactggtt tccatttcct gtgctttgat 120 ctgagaaggc acccagatac caacactgtc aaaggtggcc 180 ttgctttcag catgcaga 218 <210> 44 <211> 589 <212> DNA <213> Rat <220> <223> Clone #46 (MLSS-x) <400> 44 ctcagaattc aacczcat.-- tggacgctrtt- caagttccta ccaactgaat gaa'-aataat tcatattcac caaggccgtc ctcatctgcg cactaagccc tcagaaagcc caaaggagac cctgtctcca ggaggtgtgg gtgctgtgct gtgttcgttc ccacatttcz tctccagatg agatatgtga tactccgcga aaagatttct tgacaaa-zg gtgagttgtc tcttcttcac caacaqattg acttttatga accagttcaa zcgttatcta ttcctgtgtc aagcac tagc ttttttaact tccccagctcg acccaaccct cctcatgtt-c qt tcat ggtc ggtgcacttg ctaccgagtt cagctcctgag ctgtgctact agtaacatgg gccttcagca ccagaaggag gctacaagaaa tctggctact accgtccatc ggccttggct ac tgaatgtcg attcacta~c cctcgccggt qcgcaaccc gtgagcacaa aatcccttcc tgaaactcat ctgagcaaaa ccttcttgct gtcctcccaa gcatccgcat cttccaaggg ccccttagct <210> <211> <212> <213> <220> <223> Clone 44 (MLSSH) 22/115 <400> aaacacattc tttctttcag aatcctgatt acatatLaaat caagcaaaca gttaagacta agT-cgatarg tagggaaggg cagaragrctg ttttttttaa tttaaaaggc ccactttatt tttaaaaaac ctctatctac ztaaaaaacag 120 caggaatgcg gctcctagtg acgctqgaagg 180 tggggaggga ggt

22-3 <210> 46 <211> 271 <212> DNA <213> Rat <220> <223> Clone #48 (MLSSH) <400> 46 acaagctIttt tcatcatatc tgtcaatcag cca'tctctaa tttttttttt agactcattc cagtaagaaa tagctgtgat ctcaggccca tttttttttt taggttgttc ctccttaaag tttkkgtcca gatgaaacag tzttgtttat aaaatagaat acatgatagc tattcagagg ggtaagattc tgavtcctt gacatcatcc aaaaaagaac c ttrattttgg tctagaaagg agatctgtca aagzbctgag <210> 47 <211> 201 <212> DNA <213> Rat <220> <223> Clone #49 (MLSS4) <400> 47 ggcgtcagatt agctgaagtt aacaatcgcc aggaagccag gzcagctgga ctgcataata 120 cycgtcttca tttattgaca ttacttagca atttattgga caaaggtcaa acttttgttt 180 ttattaagca cattccacag t 201 <210> <2 71 <212> <213 23/115 <220> <223> Clone #50 (rMLSSH) <400> 48 accaagactg ctgacctgtt cgatattttc ag~cagtctc ccaccctttt cagcaaacaa attttttaca accagccct t tgtcgttttt taccaaarntc aacaagttaa acttttttag gkcctcattg cttcaaggcc ggaagcakag cagtgktzta caagccaatga ggggaagtgt qtcttaaaac tagdtttata ctccacagtt ccamtttcct ctatctcccc a"tcaattamt cgttaaatca gtagtcagtt agtttggtat cctgtatatc actcaagtta gcaaa IND <210> 49 <211> 404 <212> DNA <213> Rat <220> <223> Clone #51 (MLSSH) <400> 49 acctgctgct actacaccgc cacctcctat tccgaatgca cctaccagct ctgtgttaca tgagctgacg gccacatcct ctactatccc tgcct tggc c gggggt ccc c ggct-cctagat agcccctaag Ltcccagcta cttgcc tact agccccccag tccacaccca tacacagc tg gactacgcca gagtgggtgt acaaaccctt acccagggcc tttctcccac cttcaatgtt gtatgaagga ctctcgtgcc gtttgtagaa cctgagtcca aaccactcaa zactgtgggc gtcacagcca tctgctcagz tgtcqgtgac cagaaacca gagt crzctacatga t acctcacca ggagccctg gtctttcaag ccacctcgca agaagcagga <210> <211> 440 <212> DNA <213> Rat <220> <223> Clone #52 (r4LSSH) <400> acttc-agcag tcaaggaaag aagagagact gcagccctgt caattatttt ggtttatatt agcttaagag attatttttc ttggaaacag tataagcaag ccatgcazaa aaggaacagz 120 gta-.tccatg aatatctaga aatttctcat tactatzaggt aggggtgtag tctgggtaaa 180 24/ 115 atgaal--attt ggagctaaca ggtaatttat ccagtgatta tatttcctta actaagtcat 240 aaaaactt ttggagtato tgcatagtat tggccactga ggagcaggac ccatctggca 300 tacaatgagg agcctgcctc agcat--ccac atctcagtct cttcactgct ctcacaaaga 360 act!-gagtac cagtcagagc tgagtcaggt tccacagtag qctaatcatc tttcaggctg 420 tcaaaagaag catcagcatt 440 <210> 51 <211> 224 <212> DNA <213> Rat <220> <223> Clone #53 (MLSSH) <400> 51 acaaaggaag cggcagctgt gaa tttggag ttccttcgca aaataccaac caacacagga tgc agttcta gctgaagatg gagacagctga cgagaaatga tagtccgagc tcccgtgctc gcatgggtgc acaggagcac agtggtggt cgtcggagct 120 cttctacatg aactgtaatc taamcctaaa atgctgatac 180 attagccact. qtggaactga tcag 224 <210> 52 359 <2 12> DNA <213> Rat <220> <223> Clone #54 (MLSSH) <400> 52 acaagctttt gccttttacc cttacctcat tttcactgta t ttagzatta ctcgaaaata ttttttttt cagctcaaaa. ttctgatatg acaaattatq gactattttg atac aqcat t tttttttttt ataatttttt ttaaaaggatc aacgcaagtaa gtattagatc catactgaca tttaaacatt agrccaataag ttggtatcta tttttatggg caaattatag tgacagctta ggtgataatt aaacaatgta ttaaagagaa ttgtcttata aaagtaaaga tgagagctag caggtccact gatacagcaa caaataagta. ataaaactat. tca&acctct atattacaa. <210> 53 <211> 283 <212> DNA 25/115 '213> Rat <220> <223> Clone #55 (MLSSH) <400> 53 ataagaaaca atctaLtaaa zggttgtctt atagaaagta cttatgagag atgtagatac gaaaacaaat ataataaaac aagatcaaac ctagatatta agcaacttgc ctcatttctg atatgttaaa aagatttggt aagtat:ztca ctgtaacaaa ttatgagcaa gtaattttta 120 tatt--ttgggt attagactat tttggtatta gatccaaatt 180 ctctctcgaa aataatacag catccatact gacatgacag 240 caaataatlza aactgcatta aaa 283 <210> 54 <211> 628 <21-2> DNA <213> Rat <220> <223> Clone "156 (MLSSH) <400> 54 actgacgggc ttactacctg cccggctctc gagaagaatg attttaacga tacaaatttg agggctcgag ctcaatattg gaagctctg cat cat atgg attgccggag agcttcacgt aatgcttcta ctgacctcga actccatgqtc tgatctcaga aaagtagcac gt ttgccctg ccaagggtg ttagacttgt ggac cgttac ggacatccaa caggcagatc :tcctttttc caaactggat cagatacgga gccctacaat ttgcagcaag gcagtcttca tqcagctctt. aagtgaggag atcgaggttt tgagqtgg tiacat cccg gatcttcgaa gttgcagcca gcctcccaag cacagatttt acggagctta gatcaagata tgtctgaatg cacagagat-c acaaagcagc aagcttccaa aaa~aattcaa tggcagagag gaagacat cagatccaga tcgatggcaa t z.gcaaggtt ctcaggggcq tagccctgca aaagcgaaga gaagaatgta gaagtgttgc cctaaacttt ggggaacata gagagtaaac cacggtggtg cttcaaagga gaggaacggg gaggcacaaa ctttclttaaa <210> <211> <212> <213> <220> <223> Clone #57 (MLSSH) 26/115 <400> acaaaaatgc aacccccagt ctgggcctag tcaqcagtaa gcaaggacct gtagtgaacc =aaaaaaa caggaactgg cctc=gtaaa c agc taggag cgaaccgtca ccagtgtagt tgacttttca gcctcttctg gccaagtgcc gcctagaccc tgzataacaa ctgcttccct cattgaaagc tcttggtct. aagtgaaaag tggacagatt tggaagargca tcacctccga acataaaact ttgt taacag aaccagacac gctcaacczt aactgaccgt gaatcacaag attagattt-g ggagaagatt c ttgcagact caggccactg ctctgtccct ggaggtgatg taAaaaaaaa <210> 56 <211> 371 <212> DNA <213> Rat <220> <223> Clone #58 (MLSSH) <400> 56 accgagcacc gzzatttaca t zctgaaaa ctacaggttt tcaatgtcct tgccccatta tccatgagac ttagattaca atacataagt tatataatgt gaagctggcc atggtggtat tgaagaagtg cattgttgaa ataattctct gaaagaatac tccactcttc ttcctcaagc caaggcatag ttaaactatt tgtataacag aatacaattt aacattttaa atcacctat.a agccctcacc ggaattaata tgatttctga acaaatgcat aataggaaac aaatccacta ccccaccttc tatgtatcat attccagtga cagcactztc caaccaaaag gttt-cacaga aagatzatga <210> 57 <211> 207 <212> DNA <213> Rat <220> <223> Clone #59 (MLSSH) <400> 57 aatattttga aataaataa ttttttttt: ttaacattac agataaacatt tattaaorctg caatgttcac tccaattctt aaagtcgatc tacaaagacc tctaacatca agccagtgaz 120 gaggaatgta tccatcactt tgcgaaaaaa tactaagrccc gatgcttttt 180 attcgtagaa t-cagctt 207 27/ 115 58 <2113> 339 <212> DNA <22.3> Rat <220> <223> Clone #60 (MLSSH) <400> 58 accatcattc gc ~acacgtg aaagggaatt raaaatczca tgat-taagtt caaactgttt acaggaatga aatgtaaatg tacatggcat caaactt-act tttttttttg aaacatcagc acaaacccaa aactaattat aacaaaaaat ttaaaggatg gttlzttzttt ttaaccccac acacuataaa attatcatac acacaaaatt cagaacgcac ttgttttttt atgcatggt ccttccttta atcataagaa taatcaaaaac acaattctct ttgaaatgat tgacttaagc gttttttttt tctctactg <210> 59 <211> 363 <212> DNA <213> Rat <220> <223> Clone 461 (MaLSSH) <400> 39 ggtacaagct cagcacaatt aagtgatgag cagaagcact aacaggtgtt caggctggca cgt tttttttttt cagactggtc agttttz-gtg ggaggccggg ccaggcc-.ga tcacaaaggt tttzttttzt. taaggacaca gccataggtc cgaggacacc gtgccgccaa. accacctgaa tttttgcaaa aagcatccgg cgggcagcca toagactcag ccagcttggc gagtgggcaq gaataatcac ccaactcata tcacctgcaa gaagccggga tggaacaaat agggcctcgg tttattaatt agagtagctg catccactcc actctgtaag gctgtgagaa ggaggagcta <210> <211> 538 <212> DNA <213> Rat 28/115 <220> <223> Clone #62 (NfL.SSH) <400> acttttcagc ttaacctcat aattaaacaa aaattttctg cctctcatag ottcttcaaa aaaataaccc tatt-atttta ctacacttag tgagggaggg tcaaaactta aatcttgagg cttcataatc tct~taaagaa tttcaaatgt atctcacctg agacacaaaa gaatcaacat gatcacagtc ctgcatgttt atctttttaa accaatgqtt atgtaagtga qtctccccct. caacgttcag aaatagctgt gagggtztca tacagactca ataaattcac ttcttccatt ataggttcaac aaattacagt cccacctctt taacagcaat ctagcaatct agzttcctcc acaaatacag ataacttttt ttaactacat ttctttccaa cagacatctc cacttgtata qcctqtcaca agtttaggca ztagacaaga aaattgatgc ctgcaggctc caattataaa aaggt ttagg aaataagcta aaactttaac agttacraaca tttatacc <210> 61 <211> 688 <212> DNA <213> Rat <220> <223> Clone #63 (MLSSH) acr-tgggctt aagttctgcc gtaatccctc gaagcacatt gcccaaggtc tgataaatct gz:taaatccc aaaccaatga tagtqtttag acacacgcac agcatcagac tggagctcct ztzttttgzg tggcatcagc cgtagctagg cttattgcca tctgcacatt ctgaatatcc ccatgaagta cttcttcaca tttgacacag atatgcacac ttagctatttt. cacctgtgaa gttttaacc aaatttcagc ac agacaagg cgcggacagc tcaaaccttt tgtaattaaa attatttccc gt ggac ttcc taaaaagcca gttagttggg ttcgcaaa atttttzIttc taagaccct cagttgcatc agaacctgtc tatagcagcc gcz-gttatgt. ttcatttctt tgtttttagc tgc~tttgtgL ttccgagtga aagc tgattc tttttctctc gtcactggac ctcc tgtgtt tttctgtcct g~atggcttga cagcttcttg gtgacagcga tagggatttt ctcaggc tt ag acatggcgg tacgaatata tttccttttt aatttccgat 120 ttgctctttg 180 ggtggcagaa 240 ccgactctcc 300 tctgcatctg 360 -ttagtgtgca 420 ttt'crttttt 480 acgttttata 540 gcgcgcgcgc 600 tagggaaaaa 660 688 <210> <211> <212> <213> 29/115 <220> <223> Clone #65 (fLSSH) <400> 62 at-ccqatccc tcacactcaa ttaggctcag agtocataat, gcgtgzctgt tctgcggaac agtaqgcaqt taztttccgt ccggcttctc gtgcgcgcct ccacctcatg gaagactcga tagacatgga catgagcctc 120 aactaccttt tcggttgtga actaaaggct gacaaagat. atcactttaa. 180 gatgaaatga 200 <210> 63 215 <212> DNA <213> Rat <22C> <223> Clone #66 (MLSSH) <400> 63 acecacacag ctgaaaagcc ttccaatcat cactttaata cactgctctg tcccgcttag ggttcagagt tagtctgtag tctggcwwwr gcctaagtgg ctgaagctgt agccatgtag gcagggtctg agctattcgca ctat-cacact at-atttctgc 120 cctagtgaga gtgtaaacaa agatgaaagr vvtgttactc 180 tatcatacac atcgg 215 64 <211> 403 DNA Rat <220> <223> Clone 467 (frLSSH) <400> G4 acaagaccta ttcaaatgct ct-ctgtatca gcagzgggga Iccccacact actggattaa :-t-tglcactg gaagccacat atacaattag gagccagcta aaggaagctq ctacatgact gttcagatat aaaaaaaaaa ttagactcct ccaaatcttt aagtaagtga aggggtttgg gatigtagat tataaagttg aaaaaaaaaa tgtggctctt aggtgt tgat atgctgtaga atttaaaaag tgttgaggag aaaaaaagct gggacactta tc--caaataa cttatcttaa ttzt~gttttgt aaagaaagaa atacaaatta tgt tcagtgatga aaaagtatgc atttgctgta ,tttgtttttt aaaaaagaaa caaataaagt 30/115 <210> <2121> 292 <212 DNA <21.3> Rat <220> <223> Clone 468 (MLSSH') <400> ac=aaataata gzuttgatca tucccaatct ctatacgcct gtaatcgata agcacat"tt tacctatctg cttgcaaaaa tttgagctat aaatggtgat aaatg-ctgac cagcaaaaat cttttgctaa gtgtccaaac aggttttcca acttgtttga attatggttt tccccttctc 120 agtaaaagtg ggatctgc-ta gtgaactgag caaaaatatt 180 gtaacttaat aattggatac ttgatcattt gttttattat 240 gtgtattaat gttagttcaa ccataaaaaa am 292 <210> 66 <22.1> 380 <212> DNA <213> Rat <220> <223> Clone #69 (KLSSY) <400> 66 tctagatgca ttzttzcgcgg aactgccItrt aatacttaaa aatEtttgca tga-catcctc tttaaggcag cgctcgagcg ccgaggtaca cat tcacatt acggtgcatt taagttttgt aaatgctcct atgaagcg ct gccgccagtg tqtatatgta aagctgcttt gataaaatct ggcacagggt gaattctagt tgatggatat tttaaagact: caaaatttaa aagag: tttt agccctaagt tgtttctttc ctgcagaatt gtttactgca aaaaaaaaat tcagttttgt atccctcctc attagcacgg cqgcttagct gttactcagg taaaagaaaa tttctaggta agt cc cgc ac gggagagtgc <210> 67 <211-> 714 <212> DNA <21:3> Rat <220> 31/115 <223> Clone #70 (MLSSH) <400> 67 gcatgagacc tagttccaat gcgaaagata gtgttcagtg tgct-gtcgca ggaacatgaa Lqgcaccttc atgtggattt tgatgatgac tctagacgat aaatatttga gagacagcr.c cgtcagaaaa cagcctgtgc accagtgact t cggtgCccca actgttttac attgaaaaat ataaatgatg gatgatcgatg agtcgagatg agccatttcc aagaggttca ttttggaaag acatcatgac tggattttcc zaacgtattc ataacaztcc taataaaaaa aaatttttgt atggagacga ataaagaaac tcaatgtttc gaagagctga aactgaaacc ttctgtgagc agcacaagtc ttggtctccc ttatatagg ttataatga ggagttggta tcctgatgaa ttgcccacct cagataaggg cgaagttaac ttaaatcaag tcattacgcg atcccgttaa ttacaacaga gat gaag tt c aaagtgcatg aatgctcttg agagaagaaa cggaaaattt cacaccagaa agac~atqtt aatggaagca ggactaggga agaccctaaa attttatg tggatcagga gagacagaga gtcaatataa aacagaaaga cczgctgata gaactgaaag aaaaatataa agaactcacg Sagcaagcag ttccccggtg ctctacctcc tgaa <210> 68 <211> 389 <212> DNA <213> Rat <220> <223> Clone #71 (MLSSH) <400> 68 actaggtata agcagaggtg tgatcaccac aagctgtatz agcCttaagt tatttcattt aataaaaaat accgagagc t aztctacgag ccc tgut a ag tgaaagact t ttgaacattt tccat~acagt cagttactta -tcaagtgaa tggacaacat cattcccatt caccctttaa agctgacctt tcagttgatt gtccttaat gcggcaggtt catcaaagcg tgctgttgaa agaagactat ctctgttaaa tacaggttca cttttgagtg gcaccaagga ctctggacca ag aa ttgc tg cataggtcta tttctcatac cggcggaagc aacgtgtccc gttcatagca tgtccatcgac atttatztc tgtgtattaa <210> <211> <212> <213> <220> <223> Clone 472 (MLSSH) 32/115 <400> 69 acaaagaaaa ggtttttata ggt-ggtgaca gtagctaatq ctggtagctc caggcaattt atgagagcaa cttattactc ccacttcgaa gttcqggttt ccaaccgcac ctaaccccgc gqtgaaaga cagaactgga atgtgccgtc cagttgaact tgg'gtaaaga aaatagaccg ga-.ccattca ttctttccgc tcatccgaaa tgcatatgaa agt tgaagaa acatctgttt atatgaagat agacttgtcc tcZtttttaac ttagcagtaa atgcttatta catataggga acagccaaga ttcaatgcca cacatgctat aaaaaagaag at taagataa tacatgtacc cattcaatat accagcacac gtatcgatcc tgctttgtga aagcaccaaa rtgagttgtt gctacccacc qtgacctagg tcggccg ttcctggatc ccttctgttt cacctgtaat acactattac caaacctat: c aaca act cg tgttaaaact tggtggagtc <210> <211> 201 <212> DNA <213> Rat <220> <223> Clone #73 (MLSSH) <400> acccatgcca gtccatagca attctactgt tttaccaacc tttttctcta cctcctgttt gcgtgatgtt ccttgtatag tgccactgga gahatgcccc aacggtatgc cgccactaac 120 gtz-tctctgt tgcatacctt atgttttacc attaaagact cttccctgcc ctgtatttgg 180 ttacqtagag ccacattagc t 201 <210> 71 <211> 227 <212> DNA <213> Rat <220> <223> Clone #74 (MLSSH) <400> 71. cttacctcac t-gcttttcct ag-vdddgcac ctcctccgcc agcctcctcc tcagaccgct r.rzcccgcga gccgaccggt tctgtcatgt cgaccctcag tcccaacgtc gtgaztagtg 120 atgatagaacc aagtzatgac ctagatttat tttgcatacc t-aatcat.zat gctgaagatt 180 tggaaaaggt atttattcct catagactca ttatgggcag gactgaa 227 33 /115 <2 10> 72 <211> 189 <212 DNA <213 Rat <220> <223> Clone 475 (MLSSH) <400> 72 accagtt~gag azgtcatcga cctggaggtg catgggcgc acgctctacg gacattcgac tcccaagccc atgtctgcac gacatagaat accgaaagaw gtgggacagt atcgctcgac tgactgtcaa cgctgacgta ggatattact 120 ctgaagaacc gkgatgtcat caccctccgg tcctggtccc 180 i89 <210> 73 <2lfl> 616 <212> DNA <213> Rat <220> <223> Clone #76 (MLSSH) <400> 73 acaaaatgga cc-ctgacatc cggttttgtt g9ctggctgt ggggatggga ccaaactgct ggcaaagtta acattccatc azgagccgtg agaaggagaa ctggzt-gtt caaggggaaa tcctcaaacg t gtatt ct ct gaagttacac qcctcccagg accaggaggt gcaagggcaa actcgattaa ggccaaatcc atttaccttt ttgttt catctattgt cctttgaaga caccatggcc ccggcatgag gttgccagga ttatgtcagt caaatagaaa ggctgtagag tgtqcccact gaggacaaga gttggattag gtgaaggtga cctatttatt tgatgtgtct atcgggcatc tgttcagcca acagaactca aagacaggaa gacccttIttt cctcctcgtg cccctcctt ttcaagcatt tatgtattag catattaatg czttgataaa aaagtgcatt agtccctgga tgggcactga agccagctcc atnqgtttct aagagaaata gt.agatgacg atccacaagc gtaaggc tgt ctgctgggaa tatatuctgt gggaggacgc agcatcagcc actcattttt gcccccctgt <210> <21-3> 34 /115 <220> <223> Clone 477 (MLSSF) <400> 74 actc tgt tag cgccgagctt gccaagctct gctgatgact gaggtagaagc tt agtgaagc cagcgccatc t z.ccaagtg cttggtgagg ggggaaccac tcatcatcac ttccacactg atgaacaggt caggtagcaa tgaacaagct ttaaggaaca gcqccaagat cactgtgta. tgtag agctgatgcc catcaactct tggc cgactIc caagaatgta icctgrgagac aggccttcctg ggaatgtcgc cgacaaccat gtctgtgtgc atgtgtccta ttcagcacag taccctgag gctgattact aagaccctgg aaccagttcc aacattgtgt atccccatct tgtggtgaag tcctagagt agctttccaa gcttggctca acccggaata aggaccgatt actttggtgt ggattgctga tctacragttc cctctggttc tgaagcagat ggaggaccgt gctggctcg caaactgctt ctttgaacat cttttatgcc gtgcattgcc cgacttaagg acttgtctga. 120 240 300 360 420 480 540 <210> <211> 523 <212> DNA <213> Rat <220> <223> Clone #78 (MLSSH) <400> tagCatttaa gtztraaatag gccagggccg t ctgacaata caazcagc acccgtgaac tgtgactcag gcgagcatga aa t gctgca agtgaaagct gtc-agtggaa cttacaaact atgagttcac tctctactcgga catgggacag tattctgtga gcaaatgctg catr-tttata tttcttcct aagttaagaa ctcagttttg tccttggata cccagctgtc actcaaaccg gacatgggat ctttataaaa gtaaccgtcc ggtttgctag agcggtggcc ttt-tgttttg aggttgttaa aacactgttg tagcactggg aatattcccg cat ttgggga accataggact tgttctgcgt gtgttacgct ttlttttata tgagggaaga cattggggat catgtcgcct acctacctcc tcctcagcag tca gtcttcttta ggtagtgaag 120 acagtcccac 180 gcccttcaga 240 taagtttcca 300 aacaatataa 360 acgggtaggt 420 aggagtatttz 480 523 <210> 76 <211> 304 <212> DNA <213> Rat 35/115 <220> <223> Clone 479 (MLSSH) <400> 76 aaagcagcaa tatcaacagg atcctgtgtg ggcgtttaat ga tgactgaa ccta aggtccaaaa aggaanagtt cacagaagta tggttggggt gattccacgt actgtctaaa atgaagtgct catgg-:caac ataggatcct agtg-ctgtca aggctgattt gggcaacgatt gttttgacca 120 agagaaaaaa ttgcccttag cagaagagtt aaaaaacact 180 cacrataagaa gaggagtgac cattagagcc gactgtagat 240 taaacaatcic cttggatgga qttggaattt cttttaataq 300 304 <210> 77 <211> 298 <212> DNA <213> Rat <220> <223> Clone #80 (MLSSH) <400> 77 gcagtgaccg gggacgqcaa atqgaatggtg atcatctgta gcagggcgtc accagcaggc agccagcgac gcatcacagc cttcagcagt ggtttgccct ccttgtcctt gtcctcactg 120 tccagcttga tgtccagctt ctcgatcagc ttggctgtct cctccttcct gaagttcata 180 gtggcatcaa acaccttgaaa gatggggtcc aagatgagct ggcagaaggz gcggggaagL 240 ttcttcccgt ctaggctatt ggctgacttg ctgaacttgc cg"tggccgg gtcaaagt 298 <210> 78 <211> 534 <212> DNA <213> Rat <220> <223> Clone #81 C(ULSSH) <400> 78 actagtctta gatatggata tatacaatat acacaca"'gc acacaatccc gcttctctaa agctacctak baaat.:cgaa tccacgggag tatatcccac agtccactcc ctgcctctcc 120 ccctcctcgg ctacttagaa aagaczcaaa agcttggagg ggttt-caagt ggcagctggt 180 agaactgaag gacaccaag caatgccaca tcttacacag gaagagggga aaggaaacga 240 acaacgt-cct cctaggacac aatccatcaa ccgtgtggaa aaacccaagt ttccataggc 300 36/115 acactgaggc acttggctga ctczagcaccc ctccccctaa gtccactccc atttaaccag 360 aca ctactga gaagaccctt ccttcccaat ggctaaatcc cggttatgag aagctatggc 420 t =czaacc agctgtcact tggaaaggca ctagggcaga agagaaaaag aaatcaggtC 480 cccaacttac caccattggt aagggcagcc cagggagt atcctctctct cccc 534 <210> 79 <211> 508 <212> DNA <213> Rat <220> <223> Clone #82 (MLSSIJ) <400> 79 ac tggtagag cagggtcrcct cgtcgttggc ggctagcctc ctgaactgcc ttcagctgct gaat gatagc gcattatcta accctgc-:a ctgtggctcg ttggaaacat atcgcagtag ggccttacca tttggtggtt taagaaactt tggcaaggrgc ttatgtaata atgtaagcaa aattccaaga gtgtcgtgga tgaacacaac qctt-ggtga taagataaag aaagcttgga aaaatgagaa taatggaatc gctgaaca gttcgaggtg ggccgcatgt tcagaaacga tgtctaaagg tttaaagtta atgacatcaa accaacagcg atcaaggcct gtqgcaccca ttgcaccaac tatgccatct tcatcgtgtz taaaatacc aaaagtctat gatccagcgc tcagaaacat ccgttctggc caaaacctgg gttctgccct gaggaagrttc aaggaggctg qcctcccaga. agggtaccct ccctggtatt <210> <21 369 <212> DNA <213> Rat <220> <223> Clone #83 (MLSSH) <400> taggtctccg ct-c!gcccta aacaaat tta gggactcaca :czaagtccaa cagttgctgt aztctaatt ccatcatggg ccgccgtatc caagttggcc tagtgtggca aggccttgcc c agaaagc ac tcgcatgcac ttgcccacat aagaaaggc c caggtccgtt cctgatcttc ctgakaggaa gctcccggga aggcgtaagtg tgactccttc ttgtgaccg ctgaggatct cagaaaagat agggcctgtc ccattcgtgt nacgtctgac gacgtgaagg ccagataggt gtgattcgta aaataaaatc ttgagaatccc ctaccatttg atcaagaaag aaggatgcta aattccgctg 37/115 <210> 81 <211> 196 <212> DNA <213> Rat <220> <223> Clone 484 (MLSSFH) <400> 81 aCt~aagcagg cgacagtcta at zctcjct tc ttgaaacgct attaccatua aacccagctc acaatgatag ttagcc caacaacaca. tcatcagtag ggtaaaacta acctgtctca acgcttcccta ttagtgggtg aacatccaac gcttggttga 120 gaagagccga catcgaaggg atcaaaaagc gacgttcctt 180 196 <210> 82 <211> 182 <212> DNA <213> Rat <220> <223> Clone #85 (MLSSH) <400> 82 act ttoaatc aaggatattt. attagattaa at tggatttgct. gctcczttc-. ttactagtaag goaccagota cttaaaaaat. aattcat~tbt tttaacagaa tgaagaaagt ttaagagaca tgatc~ggaa 120 actc-Itgaac tcttatacta gaaaaaaatg taaataaact aatgatataa 180 182 <210> 83 <211> <212> DNA <213> Rat <220> <223> Clone #86 MSSH) <400> 83 acttgtacctt gggtggggag 38/115 <210> 84 <211> 195 <212> DNA <213> Rat <220> <223> Clone #87 (MLSSH) <400> 84 accgtcctcc cattttgt-,t ggtagcttaa cctatgtcaa t'zaatcaaaa aaaaaaaaaa aaaaaaaaaa aaaaa ttagaagatt aaatccaca tgtgtaaatc tgcctaaata aatgtctgca qcaagtttgt caataaagtt tagtcctttc 120 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180 195 <210> <211> 238 <212> DNA <213> Rat <220> <223> Clone 488 (MLSSh) <400> attcataaaa ctttttttcc acttacatca actttaatac atgtgttctt aacaactatg 120 cttggattgt tcatgaaaat ttcataagac attaaaacaa agctacccgc catctcaagt 180 tattccctg t:taactattt ttacagcaca tgcatgttag qcaagtatca aaaagaga 238 <2-70> 86 <211> 163 <212> DNA <213> Rat <220> <223> Clone #89 (MLSSH) <400> 86 caatactca attctttaag aaatgacaaa ttttagttt: ctactgttca aggaacac 3 9/115 t aagccccaq caacacgtca ttgtgtaaag agaaataaaa gtgctgcagt aactaaaaaa 120 aaaaaaaaaa aacaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 163 <210> 87 <211> 220 <212> DNIA <213> Rat <220> <223> Clone #91 (MLSSH) <400> 87 acaagcrt'tz ggccagctac tttacat-aca atttagttcc attcgctcac acatgcgctt ctaagattta tatccaaaca gcatatggta 120 atggacagat tagaacacca aattatgaac c-ttggctgcg gtaagactat 180 acattaaatt aaatacacaa tagtctttac 220 <210> 88 <211> 199 <212> ONA <213> Rat <220> <223> Clone #92 (MLSSH) <400> 88 acctcagctc accagtggga gtgc--tact gtcaaaacca cgagagactt ggaccggatc cgatacctga ggarggaca atccctcaga gagtcatgga ccagcacaag ctcagcaggg cagytgtggc acgcagaaca ccgacrggatg c~caagqaca 120 gaztgccagg acctggaaat gtakgggatc actatttcgg 180 199 <210> <21'2> <213> <220> <223> Clone #93 (MLSSH) 40/115 <400> 89 actatgacga gatcatcaat gctttggag ccttccacct gcagcagatt gccgctgcgc cagtactgcc tcaggattca gaggatgcac cacctcctgt agactataga gtctttctcc aagaccctgc agcccaaaag atgcagttgg tcgagaataa ggtzacagac ctctgaccat 120 ccaaggcttc tggagagcgt gtggtgaacc 180 tgagcaac 218 <210> <211> 214 <212> DNA <213> Rat <220> <223> Clone 494 (MLSSH) <400> acztcctatg ggacacaaaa tactgtcatt tgctccaaac tgacatccaa gtg-cttgsrtg atgaaagcgg agatgactca cagcaagtct ggqaggagga tgaaacccga gggggcgatc 120 cagaacaacg acggtctgta tgatcccgag tgtgacgaac aagggctctt caaagccaag 180 cactgcaacg dcaccgccac gtqctggtgc gtga 214 <210> 91 <211> 218 <212> DNA <213> Rat <220> <223> Clone #95 (MLSSH) <400> 91 gtgzaaagtcg zgtatgcttt caagagattg aagggtttgg gggttttttt tgtttgt-tgg tyggttc-rgtt g-gttggttgg ttttaggag-tt aactttttat acccacttca gatat?-tcag 120 qcaaccacat tgtagcaatc c-taaggtggt atrzgaagcag gqaggtqgca ttagtttcag 180 ggctggggag ccaatttaaa atacctcagg ctatttac 218 <210> 92 <211> 250 <212> DNA <213> Rat 4 1/115 <220> <223> Clone #96 (MLSSIR) <400> 92 acagagtctg acratctcaac ac tgacaac c gcaccagatg ttttattg aatggaccga tgggacccgg ctggtgacag cagtatcttg tgtagaaaca aggtattctg ttgctgttga aatgagagca atatcaccac cacgcacaac ccaagcgcaa gahaccttaa 120 aaggaggttt tttgctcgtg ttaggattt acccaaagcc 180 agtcatcttg cagaagaatg tgtctagatc acattgcctt 240 250 <210> 93 <211> 2-74 <212> DNA <21-3> Rat <220> <223> Clone #97 (MLSSH) <400> 93 cgcaggtgat gatacattga taaggtcaac tttaataaca aagttmgcca ggataymgca gttatggaca tgggc taggg tcaaggttaa attC awtcgcttcg agcgcoccgg cagtacagcg tctgactact acttggagaa acttgaaggc caactagctc aggccaactt 120 caatct-tgtg gtactaagtc mcagttwcwt attccttttg 180 aacagatcat ttgtaatrtgt tagagacgag ttgacttccc 240 254 <210> 94 <211> 563 <21-2> DNA <213> Rat <220> <223> Clone #98 (MLSSH) <400> 94 cggrgcaggta agctaccacc tgcgtcccct -"cctttgagg aggcc tggga ctgtggtccc cttcttgttt cactcctgca agatqtgaca tgtgtgtgct cactgtctac tcacagaaca gtgaccttta accgagcact c ac aggc ttg gtggtgctaa tatcttggct tgcta~rtgc cgtgttcttg gaqaaatgzg gtgcctgvgg ctgggactga ttattgattt cctetcaacc ttaztgatgta gtaaggcaga tctgctcagt gaggaccaga agcacaccaa tcataggtcc gaaagaattc agctaaactc tggctgacac gtcagtgggg ggtctcctca cgcttgtgtg 42/115 gatgacaaaa ctgcatgtgt ggcagagtca aacicazttac aattgagiata cagttttaaa 420 tacttacctc ccagcttaaa cctgactacc caaagcccgt actttttagc ataaatgact 480 ztaacatcggg gttgrgggatt tagctcagtg gtagagcgct tacgtaggaa gtgcaaggcc 540 c tonggztcg gtcccmagct ccg 563 <210> <211> 281 <212> DNA <213> Rat <220> <223> Clone #99 (WLSSH) cttttatctt cctcattttc aagrggctagg aggcagcaag ttttttttat t tgggac ctc gcttgttccc tggagccctg atcaataaaa atttttttaa ttcagttgtc tataacattc gaactctgag qtggacttca aatccgaggc aaatgcctca cactaacacc agcctcccct tctaacttca ggcctaggga 120 acctaagata ggtgctcccc aattcccaag 180 tagtagaaac caatccttta tatttggga 240 gggaaaaaaa a 281 <2-10> 96 <211> 272 <212> DNA <213> Ra t <220> <223> Clone 4!00 (MTLSSH) <400> 96 actcctr-tca :tactctcaa agtagactaa caaagaatga acgatccagt gcaatcaaaa ataactcact. cttattgctg tcaagtagca aaggaaaact gaacttcagt ccaacaagga agaatcauca gtcataagac tgagatctgg 120 aaccgaagtc tccacagatc tatcagtgga gcaacgtgtc catgtgcttt 180 agtagtgaaa caaagaccca gttcgccact gtgatgctgc ggtgttgctg 240 cactctgact aggcactgaa gt -272 <210> 211> <212> <213> 43 /115 <220> <223> Clone 4102 (MLSSH) <4CC> 97 acctgagt.Ca tzgggtccgt aaaatgccct aoaggtttcc agagggtgca zac aagcatc aatttzttgt agcaaact ttatattatc attkdgctca ktgcagctca atcctgattc ggtttcagaa catctacaaa cgagagcgca tgtcacagtt tgttgtagga gatgactact taatttttca taattcatta agtatggtzg r-ggtgtcana tgctaccaaa gtaggaaatt c tgggagtgt ctcaatttca agctctzaat cttattcacc taggyaaaaaa aaagttcata gwtctcagag actgggatat ggttgatagc cttgctcccc tggcgtt-ttg gctgcagccg gtgattccgt atggtcttct gaaatactaa caaggg tggctrtaaaa gctci--gacca agttgtgctc tcaccacc ggtagaggac cgatcgaaaa gaggaagcat agcctacttg agcttaattc catactaaac raaggat tta aatttccctt acaaggatac g ctgtagaag cggacaattg gtaaaggtqg aaactggcgg tgtaatgttc <210> 98 <211> 520 <212> DNA <213> Rat <220> <223> Clone #103 (MLSSH) <400> 98 tttt CCC C tacacrttctc atgccatt cactgccgtc ttgggactca Cggctcttc actctccccc gcgggaccga ctagaaaac a ttattagaaa acttgtaaga taaaaaattc .gacaatgtc gaacacacgc tgacaactgt gtgccaata ggagggatac aaactgaaaa cttcctttat tttttaaatt tcagcaatat ctgcactaac tt-cagtgcaa ttccgaatgg aagaaacaac ttagggctac agcgcttaga tcttctaaac cttaaaaatg acatttgcac ccaccgactc cacttatt- c ctgagcacag agaatt.cac ctgtgccaca zttacagt aggtgaaaat caattttctt ccaagaaata ctgcacatgt cag agaaac cctccgatct gagcacttga aaacttacgc aagc aat tctC ttcaaagcac catgcagcat ccgttctact acaggcccag gcctaaagc ggatccgagt aaaaattt.gc <210> <211> <2 12> 213 44/115 <220> <223> Clove #104 (M-TSSH: <400O> 99 gaa:tgggcc cggcttabrt gcattayybm agagatctag atg tcgtaaa ctctagatgc cgtcgcgcga hchvcacata gtccacatgg g99c99 atgctcgagy gkcgcagtgt gatggatatc tacrmrdartt agtgtacagc ttttttt~tt tttttttttt agcgtccmca 120 gaaaagagca tccgaqcttc ctatatgaga gactag 2.8 tttgggtcat tarr-rvscca tcaacatgcg tatgctggtg 240 256 <210> 100 <211-> 215 <212> DNA <213> Rat <220> <223> Clone #105 (MLSSH-) <400> 100 acaagtccct cat ttcc tag cccgatagaa acacaaczac ctgccccgtc gaagatctga aagggggacc taataaaaac tcatgggtct caacctggga tgaccgcata gcagaaggca cctggctccg cccacctctc ctccgctctt tkaccttctc 120 tcagtatatg atggtcccta ccccgggacc ctgaatcatg 180 tcactggraaa ggttt 215 <210> 101 <211> 579 <22.2> DNA <213> Rat <220> <223> Clone #106 (MLSSH) <400> 101 gtcc-cctcc gtaggcacat cctgttgccc ggtctaagtc gccccacccc agz9ggggtgg ctgactgact cgctcacgat ggggaacctc ccacagaagc caggt-czaaa accgcaagcc cacccctccc gctctcagtg cccggtctcg agaaaacccg cqcagccggt tcatactccc acaagt-gtgg accactgggc ctcaggggcc gtcccgctct ggagicactat cacgttcctc ctgggaggcg aaattgtcaa caacccacag tgttgtagag tcctcccgct tcctgcccat cagaagccgc gcgt-cgctcc atatacccct ccrttttccct gttaaagct cca~gtccag gccccattgt .cacgctcca aagtcccgga gttgctaaag caatgc ttaa agagagtgtc 4 5/115 tcttcattcc agctctgcag ccggcctggg ttctaactca gcacct-ccca taccaqactC 480 aaggctcgga gaaaagaata aaggccacca gatgctgg aaaatgggtg aczagacccg 540 accagtcza gctccctgct aaccatatgt tgggatact: 579 <210> 102 <211> 236 <212> DNA <213> Rat <220> <223> Clore #107 (MLSSH) <400> 102 tggcttacct tgaaataccg agatccagtt attcgccccz gcctgattac aggatgcaag agtgggcccg ccgggaagct: gagagact~tg agaactcaac ggcctcccca tcatggaatc caactatttt gatcccagca accagaagat gactgacgaa atactgagca gggcttaaga agcatt-actt ctctgttaat ttcctggttc ctcagaacac cttattaaag taattg <210> 103 <211> 255 <212> DNA <213> Rat <220> <223> Clone #108 (MLSSH) <400> 103 accgcgtc-t tttacacaga. aaatggagat agctccgcta atccccaaa catcaaaaat qagaaacggc agtatatttc tccatttcat gatgttccaa. caaggatgtg ttccacatgg tgnctgaggt tccacgctgg tcaaatgcaa 120 tgctacaaag gaccctttaa acccgattaa gcaagacgtg aagaagggaa 180 tgtggccaat cttgttccct zacaaaggct acatctggaa ctatggcgCC 240 tttgg 255 <210> <211> <212> <213> <220> 46/115 <223> Clone #109 (MLSSH) <400>~ 104 acazqatgac ccagtagtga tagaggggag gacggaagac agatggagat gt caaga taa accacta-gga cat cage ttg atgaggttcc ataataagac cagtttaatg tccaaaat tg accctltgagc gattagccat gatgaaacat agcacaggtq aggcttgcaa tggc tgagct aaggtctata acgtaactcc ttcaaagcat acattqttat caaattggag tagtacc tgaagttcat tgggataatc gggcattttc cactgagggc acacctgatc catcttgctg tcgctgagat atggtcctgg caggaggtca caaggcatca agccttcagc ccttggcacc gtttctcgga ctqttatgaa gzcaqgac:: ctgtgaggaa tctccataga 180 aztggacaagc 240 tctcccccgt 300 aaagtaagat 360 c-laattcagC 420 447 <210> 105 <211> 270 <212> DNA Rat <220> <223> Clone #110 (MLaSSH) <400> 105 aaatagaatc acaaaatttg ttacggtag ctttgtagtg agtggtcaat atggttggag ctaatatcaa gatcaatctt tcagaatgtc aaatagtttt c tga tgttgg cgatttaaga cctgctgact aagtgactga ttagtgccct gcatagccttt cctttaccct gactcattcc 120 ttcagtactt gcattctagt tcaartagcc agaaaaggaa 180 atccaactgt atatttactt tatt-gtaaat aatggtgaac 240 atattccttt 270 106 <211> 199 <212> DNA <213> Rat <220> <223> Clone #111 (MLSSH) <400> 106 gccgccagtoc tgctggaatt cggctttag cggccgcccg gcgcaggtac aagcztztaa ncttt~tt.ttcatgaagg gagaatcaag ccaccagatt ttnacttttca tgccaaaaat 120 aaagttcccc atcactccca ttttcttaca taatacatga aatacagaga aagcagaaatt 180 catttggtga actatcagc 199 47/115 <210> 107G- 321 <212> DNA. <:213> Rat <:220> <223> Clone #112 (fLSSH) <400> 107 gtaaagcttt ggatcccttt aacccctttc aatccccccc accccccccc ttt-tttt trtttttttt cccaaaccta aaaccctttt ccc ccc ccvg tttctttbct tttttctttc caaaaacaaa aagggaagaa aagttttgaa aaaaaacccc cctggggggg cttccatttt tcaaaggktt tttgggrdtc aaaaagggtL gggraaaaaa 9 <210> 108 <211:> 613 <212> DNA <:213> Rac <220> <223> Clone 4113 (KLSSH) c400> 108 acaagctttc ataaaacaat caaaaaaatt :c:c-_acttg cautagtgca 9Zgr tgctat attctcttta tcattacaaa aztacatcat tttaccccta aacttttcag tttttttttt tt.caaagaa gagaggcaca ctatccactg ctttgaataa gtcatcactt aaaccactaa ttaattaga: ttaagtggga gtcagctcaa acg tacatttaaa attgaagtat tgtttcctgg atcgaataaa tcaattgctt ttcccagaag ctcrtat ttct catttaaaaa ctttctcccc ttttttgtaa aaccatctag tcaaataaaa gactcctcct tcacataaaa ataaaaaact gcauagctta ccacagataa :tttttttca ccactttaaa ttaagtaaca atactgattt ggtgaaggtg acaggagcct tatatacttt tcattttgaa gaac tatatg aaaaaaacaa taggaaaata acaaatcaaa .ttatcttac tatagcatta aaggtggggg tcccatgagg tatacagaaa ttacacaaaa tctaaataat tctgtgaaga qgtttataca gggcgttcag <210> 109 4 8/115 <211> 287 <212> DNA <213> Rat <220> <223> Clone #114 (MLSSH) <400> 109 actctacaac tt taaatgng ataacctaaa t tggggacac aaaatttttg ttaaaattgt atctacactt agaattcatg ttttagaagg cctaattcat gtctgatgct ttgaaaagtg tgctcatgcc ttctaaaaatg agaacgttgc aattggtt-aa aaacaaaata taaagacat 120 tcacacatat. tttattgggg gtgatgtgcc tttgatctaa 180 aaagtttgtg tttgtgatta tctttcgaaga gcttggaaat 240 catttcccat gacaaaaaaa aaaaaaa 287 <210> 110 <211> 182 DNA <213> Rat <220> <223> Clone #115 (MLSSH) <400> 110 acaagctttt aaaaaaataa gaggccaggg at <210> 111 <211> 506 <212> DNA Rat atattttaaa gatgggag-aa ttt-Itttttt tttttaacaa tacttgggttc tatttatcga gagtaaaaag mvrtgttgagg atggaaaggt ccaccaaacg 120 ttccccaggg gaatgaaaaa taaaatkagg ttgggtagag 180 182 <220> <c223> 4. Clone #116 (M.LSSH) <400> 111 acaaaaccta tcttgcaggc ccttccatat ttttgaccgg tttggactta ttgttgttcc attgattgtt gttaattgaa caggcgtatt tcacttagct tgttggagaa tgtttgctta 120 aacattccag ccttccttcc ccgggcgcag ttggattccg aattactct. ttggagagat 180 4 9/115 cacacggat gacgcctttc gtctcgagc tcttgagctt aggtgt aaga gtgtatctgc ttaaaccata t tctggatgt cgtatgcat= atggatgaca gatgctgacc agaagatgca tcatggctgt ttgaagaaag ctgcttatat ttttatgaat aacaatagaa ctgaac caccacacat. gccctggaca ttggtgccat ggagaagatg ttcgagttct atgaqcggqt ccgaccagga ggagtgcacc aggacctacc tttccaagaa cttctctctt cggattgatg tctagcgaaa taggacagtc gacattgtg <210> 112 <211> 274 <212> DNA <213> Rat <220> <223>' Clone #117 (MLSSH) <400> 112 acttgggggt gaggccaacc gcttctggtgg cttggtgaat gcccgaazac tt tggaggga tgtgggagcc caagtgcctt. tttcattgac aaagggatgc tgaggggagg tgaataattg tgtgccacag taggaagtca ggttctccat gggagtccag agattgaact caggttatga 120 cacctgataa gccatctcac cagcgctgac tcggtaatgt 180 aaagtattct tcatgaaaa catgcactgc tctgttaaag 240 tttaggaagc cgaa 274 <210> 113 <211> 488 <212> DNA <213> Rat <220> <223> Clone #118 (MLSSF) <400> 113 act tcat cc a ctaatagggc ttgtaggaaa aatttriatgg actaaaaact ataatgtaat gattagtgcc aaatttccct gagaagcc qccatgtatt. gtgtactgga caccagctta ggcttCtCgC aaaaat taac atttaaacag ggcnaaggca aagtgaagt t tactctCttc giacatgattt agagcacacc agcgaataaa cttactatgt taactgtttt gagagacaaa ccccgaggta c-tgactcaaa aaacatcaga qtggggcagg aggctacagc ggtttctctg acaatacaat ggccaagtgc tgagttcttg agaaggtcag acacagtgga catttctaca caaagctgtt attctttgag tgacgc tgag ag tcc aggg c taaataacta ctttctgttg gggac ttgac gctgtgcttg attttagaaa tccttttgaa ttcaaagggg tttacttgcc acagagtcct 115 <210> 1124 <211> 284 <212> DNA <213> Rat <220> <223> Clone 4119 (ML-SSH) <400> 114 gcctctagat gcgccgggca gctacttgta gwg-wt tgtgc ttczaacagt gcatgctcga gt-acttgtgg gacttctccc cacactgaaa ttacgaggag dbggcgcagg tgatgatatc tgcadattcg gcttcgagcg gatacggggg gatggagwga tcagagatct agctacagag tcgatacctg ctctgtgtct agcl-ggyatg gctctgcwgh gttgggactc atgavgcctg ctcccatgag cattcttctg acagatggtt tgtatagtca tcag <210> 115 <211> 278 <212> DNA <213> Rat <220> <223> Clone #120 (MLSSH) <400> 113 gtacagccgg gtoggggacac gatttgattt gtaagtctgg cttactggca accgtggatc tcttcactcc gatt tcctaa ggaggtgagg cacttgqatg atgagtgt.gg gttctgatgt cetacaccca gtaggagtgt tctggtgcgc ctggtagaaa ggtctgcact actggggatt 120 gactccaact gaaacaagac acgttaactt agggtaatga 180 agccaaggag tgggtgggca gagactctct taggtctttt 240 ttcacgrtgac atccgccc 278 <210> <211> <212> <213> <220> <223> Clone #121 (MLSSH) 51/115 <400> 116 gaggthhavb bytkwwtttt tacactgtca cctattadhy ttgagaaatq actttttata gtaagtatat ttggtaattc tggct~ctga tcccaagcct ggaaaagcgc tgcagccctg 2120 tactctagg aaacagactc agatcacaga gshbccacat tctctgtggc attgtaac:c 180 caag~t .actcag <210> 117 <211> 413 <212> DNA <213> Rat <220> <223> Clone #122 (MLSSH) <400> 117 acttaagaac t caaaatat t atacttatgt gtgcaggct tatctcagct cttctcattt gaggcctctca ttactatcag ttcttgcctt tcacttggaa agggatatgg aaaaatgaaa tgctttgttc gtccttttg agtgaccaaa g tr~rt tC taacataaat taacagttgt gctagatttg agtataccac tattagtaac ttataccaaa taaaattctg atcacccagt cgttcacaat tttaaagaaa aaattcaaca tgtcaagaag gaacgcaaaa tccgaaaaag ttgacattcc gccccgggtt gtttctactuc ttgtgcttt: cctgtztacc gagagcactt aaaagctgag aaaacacct ccatctccac tccctagaga tgcaggaact tta 118 <211> 1'79 <212> DNA <21.3> Rat <220> <223> Clone #123 (MLSSH-) <400> 118 acagakaggg ttagaacaga acccagaact tctacagaat agaaaaccca. cccttgccta tt--gcatgga razaccaccc acagagctaa taagtcttac agttatccgg aggcctargt 120 gctgctttta aactcaggac tctaattttg aztsrnmcat acat gattga taaaagtca 179 <210> 119 <211> 238 <212> DNA 52/115 <213> Rat <220> <223> Clone #124 (MLSSH) <400> 119 gggcctctag cgckgccgag aagggagcag ygchcaggag atgcvgctcg gacaggwwag gcagcgcgag tcccagtgag atnycqcagt tgatggatac cgcagathcg gchagcgtgg gtccgggcac aggagcmagc acmccttcac aaagkdacc acaggcttcc taccgagayh gggagaggag agakgg~acgt agagagtacc ttagacaqgg gaagrnaaatc cdgggcag 120 <211> 3*77 <212> DNA <213> Rat <220> <223> Clone #125 (MLSSH) <400> 120 acactgcttc ccctaaagaa gtaaaaatgc aaactttaaa ggaaatgttc tcttttgtag acgagaatggg cagcaaattg agtgzgtgac tgttataaga gttctttata agttttatgt atagccatta ttcctaa cggtgtatut aacaagagag catagaztta aaatacagca atgcagacac catttcttta gggattttct gttgccigca tcctagttcc gtggaaaact ataagctatg aactatttca cgtaaaatggg tgccagttta tt-aatttttt aacaagttga gggtaacaat azgccaatgt tgtaattttt aat-tgtctat tczttatatg acgtaaggtt caaaacgtaa atattctata <210> 121 <211> 223 <212> DNA <213> Rat <220> <223> Clone #126 (MLSSH) <400> 121 aaccttcacg gggtaagggt tctttctagt ttctatatga agtatgact. tcttgagact gzggcagaac tcagatgttg qtgtctttac agggaacgtg cttaccaccc atcaaattat 120 tcatgggaaa attaaaggtg gtttctggta actgggataa acagagacca ccaaacttaa 180 53/115 caattatctt aagggggcac cccctaatcc aabcccagcc aca <210> 122 <211> 643 <212> DNA <213> Rat <220> <223> Clone #127 (MLSSH) <400> 122 aclt-ctcgggc ttagacggcca gtctgt-accc acaggtacta cmgccacctc cagaccgaca tttggaaacc acagccacca gttatgggag agtgcctggt cccagaaacc ctgtagacag caagcctttg acaagcccca gccacacttc cacctctgga tccacaaaca acagttccaa agtgtccgtg tctggatgtg ttctcaggca cggcccagcc ggaatagaat aggaagctac ccccctctga atcccagctc aagccaggga agaagataac ctcaggttc ggctgaccca agcaaatgga acaggaggca tgctctggag agaacttcci caactcctta aggctgrctgg ttcagaacc catgttcctg aaggacaggt taagaacctg tccgcttctt aaaagaggac ggacattcta aaaccaagaa gggc-.ctccc agaggaagct caggccccta qcctgagcag gaggcgcgg6 -agtcccacac acccctacca gt7-gttcttg gaaattcctt attgavvgtc gnnccagcta actcccaaga tctcctgagg aakagaagcc gaggtcccca accagaactg ccatccccga gcatcaccga tgcagagccc accatct.gag ctt_ <210> 123 <211> 194 DNA <213> Rat <220> <223> Clone '1128 (MLSSH) <400> 123 ac:Laaaact attctgcttc ttagatagcc ggaatactca ggtaaatacq atlt-aadctca aaatggaagg tgggaaagac catggacgcc agaaccaaaa acacttcccc tacaacgcaa actgttaact 120 tgttggwact ttataaaata gttacvyttaw actggccaat agrgatcatg 180 aaaa 194 <2-10> 124 <211> 401 54/115 <212> D14A <213> R~at <220> <223> Clone #129 (MLSSF-) <400> 124 acaactgtzc taactagatg caratccatct ctcacagatg g'ggatgagtg gtttgagttt, atgaccggcc cc tggataaa qcactcagtc at tcccagat art tggaaaa aagctcactt. attttacygaa actcggcaga g-gtgggctca cagcaatgca tcccagccag cgtttcactt ggagtaggct- ttcagatata aacagcttag ctcagcttaa ggag~gggcaa catgagacca ctctggagtt gcaggacagt gqtcagaaga gccttgtttg cagaagcaac aaagcagctt ggcttcctgt tat ottt tot ggtccaetct catcacttca t aacgcagaga gtagagtgat aggacttcct. tctcactgaa tccgtccacg tgggaggacc <210> 1.25 <211> 326 <212> DNA <213> Rat <220> <223> Clone #130 (MLSSI-) <400> 125 accccazgaa gzttttaact ccagtcacta caaaacttta ggcagtggga agagycaatt tactcagaca acttcattac tgttcacaag ggccagggta tctctgagat agtgagaccc ggacacaagc aagtatgaaa agaatataca tggaggagca caaggccagc tttctt tgcaagttcg ctggagacag tccctgtggg catacacagg ccatctgttt aaagaaatac ggtctagctt gtagcttcaa aactaagtat atcottact totagcacgg gtgargcaga co-gatctaca aagtgagttt caggacacoc <210> <211> <212 <213> <220> <223> Clone #131 (MLSSH) <400> 126 115 acactttc tgr-gacagc -gotcatattt c,.ttcc--caa aaaagtcccc tccaaacaga tcccagrtctg gaaacagtga gagctggcga cctcaacaaa at tgacaac t =cattcctqc gaacccttc- tttcCttCCz tagaaacaga atactgttca aggagagaag tcaaaggcaa ccagactcag taaattctga cccacggtgg acaagtgaga ac a aaggaga aaaacttaa gccaccaaca atttcatgca tctactctta cacgagctta tga caa tgga aaa gaaaacagtt gacatttgaa gctccctaaa aacatcagta gctggggcca aactctgact tcctgacagc tgaaatgtzc actcagactc tactzacttag cagtaagtct ttgaacttcc attgagggca cctgaacaag cacgaatgaa aattagctgg agttacacca acgaatgagt tcttacttut gt~tgcgatc cgaaatctaa totcctgatt agtagraaggt cagttctCc ctctccttaa tgagt cacat gaacccaatt <210> 127 <211> 233 <212> DNA <213> Rat <220> <223> clone #1132 (MLSSF) <400> 127 actocactca cacgc-Ccttg atgrtcacttg gggagtagt,- cccatccaca catcacctta gtgtcactta ttggcaacgc catagaacag cattctacat ttcrtttgga agttacccat tcatgagtaa aaacaggaaa 120 gtaaatgcaa tctttttgtt ttaaaaccta gaagacgggt gaatgggaag 180 ctgatactkg ttgtctggaa caaagctcta atgaagazat gtt 233 <210> 128 <211> 354 <212> DNA <213> Rat <220> <223> Clone #133 (MLUSSH) <400> 128 accctacaaa cakaagacca atgtgacccg tgggcttgga ccagttacca t-tccctgtaa atgkagactc gactcaaaca aactcaagct ttattagggt gcaaccaact agacacacaa taaaggaccc agagactctt caggctcaag gcccttaaka tttatttttc cacac tgagt actaatgtcc ccaggccttt tgatcctctt taattgttaa ccawgaataa tctgccacag -gactgctgC tctttatatg gccttagtct gtttggtg-gt ttttaagagt tctcaagaaa agtttccca gagtc ttgct ccccatgtac ctctgtt-lat ggtaagcacg agca 56/115 129 <211> 4 13 <212> DNA 213> Rat <220> <223> Clone #134 (MLSSH) <400> 129 accagt-gttt tgaggcgtta attgctttct atttcctt acacgggaag cttcat-tttt a gaga aaaa c acctcaggcc gagagggaaa ggaatacac t attaaagtcc ccaagcagtc ggtttcaggc acgcagcaag agcatgccta agggtatcaa gttcaaatag aaaccattaa agctacagct tttggcccct gccttttaca tagcttttaaa tacacacaag gcttattttt caatgacaaa caaac tagga acttcattct aggcgcggtt cactcacttt gtgacaztaa agcacaatat actaagacta tatttacagc tgtaaggcac ccttgacagt ggttagttat aaactatggg zaaaataata caaggagctg ggatacctgc acc <210> 130 <211> 408 <212> DNA <213> Rat <220> <223> Clone #135 (MLSSH) <400> 130 acatgtgaat czccctccac gzt tcaggcca acacataaag ccagacttta gtgtgaggaa tctaaccggc tgattatgat gaaaacagat gctgagcagc c ac aac t Ccc gagtatgaca agtggtgcz-t at-tg-gtgtg ctaatacaat gagatcccca actaacgggt cgatgggaag acagccatca gtatcacttc cagttgttat cccaaacaaa aactgtacac cctcaagctt gcacccgacc ctgcaaaaat aaaccaaccc tcaaagtaaa agtttagaga agagttcgag gggcacacca acagtgcttc aca~ccaaaa ttaaacattt aaaaaaaa cat ttaaatt actgcccaga cc--gtcaagt aagtaaacac gaataaaat caaatcactt 120 180 240 300 360 408 <210> <2 11 <212> 2 12-> 57/115 <220> <223> Clone ii137 (.MLSSH) <400> 13'1 acaagctttt tatgacccaa ttaaataata gttagttact tgaacaz: at taatcgccgc ccaagtzta cagacattaa gccttaattt ttcttczttc c!tatgcaaac btttcaagtt :tggctatcaa gacogataga tgatazaaga atcca <210> 132 <211> 134 <212> DNA <213> Rat <220> <223> Clone #138 (?7SSH) <400> 132 acaagctttt tatgag~ccaa aacttaagat :-tttttttt ttttttttt ttttttcczt gtatgaactt tttaatgaat tgaacattac agaattaagc caaaatttta cztgctttnc cttatggcaa 120 acta 134 <210> 133 <211> 185 <212> DNA <213> Rat <220 <223> Clone #139 (MLSShi) <400> 133 gcatgtgatg tytkcratcg ctacgtgcsc gcgagtttt tttztttttg agagaatgat tatggtgttt aagcatgc'tg caaggggggt ctcagagtac aggctaccac atcacaacat 120 gcattcctca caggacatgt gcagaggctc ggggaycata agzagtcggg argtgggact 180 ccagt 185 .c210> 134 <211> 216 58/115 <212> DINA <213> Rat <220> <223> Clone "1140 (MLSSH) <400> 134 actgcggact taaataaagg3 ttttzttaag gtaztgcgqzc g,,-gacaga gactggcgzc gtcagcccgg agcagtrtcat gaaatctttt gagcatatga agaagtccg ggattactat 120 gt!tacag-tg tggaagratgt gaccctagga caaacttgg ctacagcaac tctgaccaza 780 gaacmtaaat ttatccattc atgtgctaag agaa-gg 216 <210> 135 <211> 208 <212> DNA <213> Rat <220> <223> Clone #141 (MLSSH) <400> 135 acaagcttt tccttttaaa gagt tctagt agtctcctgc tttttttttt atcttaatat rtccttttaa ctcaccaggc tttttttttt Lttcaaattg gttaaataaa ctccatactt taaaatatta ttatctca~gt aagctactct attaagttta. 120 atctttttaa atagaaactt atctgcgaat gcctcaggtg 180 gactaccg 208 <210> 136 527 <212> DNA Rat <220> <223> Clone 4142 (fLSSY) <400> 136 acacttatca tgggagtttt., tctaaaaaa tatcgtcaca tctgaaaa aaacagaaag atgrggctgtc cggaaaataa gatgccaatt ctgtgaacaa tttgtgtttg cttattttta gttttttttt aatatttttt atattttttt 120 acagctgaaa aaccctttca acgacatgct aactggttgt caccctttga 180 ctatqgtcag gatcgggtqgct aacaggctcgg aatagatgca cattataaaa 240 agggatgttc cttgtggctt ttttcttggt taagtgccta ggggcaggag 300 59/115 augggttaac aaaacactgc tcgatgatga attttctttt acacaccagt ccg ttcccaa 360 aaggccctca tattgcangt ggttctatca gaagttaaaa tgaagacaag aaaaagaaat 420 atcctztcaa ataacagagt cgacactttt tcccccytaa aztaaatcagc ataacttttc 480 cacataatgt aacaagaata aaaatacacc ttgcaaaatc caaaagt 5 27 <210> 2.37 <211> 269 <212> DNA <213> Rat <220> <223> Clone #143 (MLSSH) <400> .37 aat tggcct-c t ccagcggcg ccacttataa agacatataa ggcgataggt tagatgcatg Ccgaggcaggt acacattctt tcaggcaaca ggggaagggc ctcgagcggc qcagtgtgat artatctgca g-aaczcggct cttcagaatc tgattttaaa aacctttatc tactaaaaac 180 gttaagacta caggaatggg gczctagtga cgctgaagga 240 aragggctg 269 <210> 138 <211-> 198 <21.2> DNA <213> Rat <220> <223> Clone #144 (MLSSH) <400> 138 aagcd~tttt aaagatacaa ctaaaaact ggattttcag ,tttnt !:ttttttttc gatgccaatc aaaactttat tctgtttta aatagtcaaa aaagttacat cagctatata tgatcgccct ttcaaaatcc 120 gtatggcatt atzagctgrg agtaaaatac tactactaat ccttagaaca 180 agcctcaa 198 <210> <211> <212> <213> 60/115 <220> <223> Clone #145 (MLaSSM) <400> 139 t-vrtgattat tattatcatc atcatcatca tcccatcat tattttcaca ttttaaatat 120 tacatttcct tctttcc 1.37 <210> 140 <211> 188 <212> DNA Rat <220> <223> Clone #146 -(MLSSH) <400> 140 actrtgggctt cczttttttt tltCtgctggc cgt-acz-ag tgggctcctc ttttttgtgg atcagcaaat acctgtgaaa ttttrttcyt ttttcyttcz tccttcztt:t G0 gktlttaacct aagaccctgt cactggacaa tttybatagg 120 ttcagccagt g-caccccccg Sgtttcrccct tggtggtcct 180 188 <210> 141 <211> 553 <212> DNA <212> Rat <220> <223> Clone #147 (MLSSH) <400> 141 tactacaagc gtzkaattag tagtaggzaa taatcattac caatccacag atagaaacgg aa t ag-gaag ccctagacta aactcattga gaaaggaaat tctgccgtca cgccttactg attgctttaa t-aatcacaat tatctcccca ctttgtaaag ttactccatg azc tcagtcc czccaagttc tgyaagcctca tgggtggtca gttttgttat tctaatgaac ttcccttatt t-gcaaggtaa actattttat caagtc--ata agaaacacgt gaac-cacct ttgtttgcag gatttatatt tatagtagtt agtggacgtg aactaaaatt aacttaattt gtgtgttgct, catz~ztcaag catttaaccg gatttgctgc acaotttcc: ctaatacctt gaaattgaaa tagggcttta a'tttttgcaa ctaatgagtt ggacagtgcc ttctgaact: atccataaag ggccattttt g-ctggaaaca atcagtttaa cagtattcag ttg:zataaat gatctctgtg 61/115 aacgtgggcc :-gc 553 <210> 142 <211> 137 <2'12> DNA <22.3> Rat <220> <223> Clone #148 (NMSSH) <400> 142 tctggagagc tgaagtctga acgctgtata zttggactcc caagattgraa gatccagcat cagagaaact qtcnaaatac tggaaagtga aataaagact t wtcctttca aaaaaaaaaa 120 aaaaaaaaaa aaaaaaa 137 <210> 1.43 <211> 202 <22.2> DNA <213> Rat <220> <223> Clone 4150 O(LSSH) <400> 143 ggaacgtcta agcgtctgag ggctcgcagt cgtccgkbg ggcaacgtgg gcctcagggag tagccgcgta ctacaccatc tctccccgcc cgcgrgdtagg caaaggcgtt tgcgcttccc ccttcagtag ccgaaagtta gtcttttgca gtggagtaag 2.20 gccccgggdw ctggcctcac catgttggtc ctatt.tgada 2.80 tt 202 <210-> 144 <211> 155 DNA <22.3> Rat <220> <223> Clone #151 (MLSSH) <400> 144 acatcgctgc ataaaatgca atctaaatgt cctvttgatt ttatgaatgb bwgggcttgt INO 62/115 gct.ztacqaa cctcaagttct tzagacgaca gtagtgggag arbcattaaa gataatgaac ygg~ttgtgt ggtttttttt :tagaaaat aaatt.S <210> 145 <211> 215 <212> DNA <213> Rat <220> <222> Clone #152 (M~LSS1H) <400> 145 acatctagaa gcattactgt agaatctgag cagattatgt g-taaccaaaa taaaaaagag :ataagaaaz aatcczgaag ctaggtatgt ctcacaattt tgtagaatct tacagcatat 120 tcataaatt tctcagtgaa aatgttggct aggcaagttc agtzaaaata tagtagaaat 180 gtttatcctg gtttctctaa g9tatacatta aztt 215 <210> 146 <211> 705 <212> DNA <2:13> Rat <220> <223> Clone 4t153 (MLSSH) <400> 146 acacatgcaa attaaaaact armngttaca. aat-tttcaag atcttctcta. gtacgaatct tgtaacccat tggcctttta tttcagagtt ttcacttagt gtgattgaac cztataaazc gggzatcata. cac-.aatgtg tactactatt gtattzagttt tatataaaaa ac-aacattat aatgttacta attatcaaaa aaagataaat tgggat-tcca tcatatcaat ccatzctcag actatgaaca tgtaatttaa acctttttta cctttaatrg Ltccttttca tataagaact cctgaagtat aatttttttt ttgcagacca ttgatggtaa aaaaagaagt ttgtatctta acacttggat aatagttctg ctaatatata. actctagacc ttctacatta ttgcttgaat tcaaatttrtc gatcaaaaga. tcataaaaga catagctcag ttagtttcca atattgatia. acagattta~a tatgtatatg tattttaaca taattataca at totca tgg aattctggtc ttatggttat aacgtttcaa taatagccac aggt cagt ct gtcaaaactt aaaaccaata actt c tttactcata at:tttcaaa gtgtcaaacc aatattaaat aaaaacccat aatgtcctta aaaacattgc caaggcttta taacaataaa tgtataat ta 63/115 <210> 14 7 <211> 283 <212> DNA <213> Ratz <220> <222> Clone #154 (MLSSH) <400> 147 aatgggctcZ ttcgagcggc gccttcaaca gawggagaa t atgaactcat agatgcatgs gccgggcagg gt gagcacaa ccttcctgga cagttcctag whgaagagcg cagtrtgatg gatatctgca tctcaqaatt ctcagaaagc caaagatttc agcrcatttc aaaagagact gacaaattgt cgcttcctgt ctccagtgag ttgyaccgac gaggtatggc ttcttcacct cat gaatccggcz tttttttact 120 cccagctgca 180 ctgctgcaaa 240 283 <210>~ 148 <211> 350 <21.2> DNA <213> Rat <220> <223> Clone #155 (?4LSSH) <400> 148 taccctgccc ctgactgacc cctgag-tccg gc :ggaggga aaatgcttta gatttcctgc cctagggttg tccagctct-c aactccgcct ttttaccctg aggctgcctg tgtggctgga gttccacctg gattttattt atcgctccgt- agttcctgtg tgaatc tggc ggtaactcac ttttttagac ttgattcrttt tactggcatt tctttattca aggacagaca aargctctccc gttttttttt tctcgctttt.t ttctggggat ctcaaaatgg cgcccgczcc taatggcgct cctgtctcac acctactgta ct ac tgtgc a cttgtcccga <210> <211> <212> <2 13> <220> <223> Clone #156 (MLSSH) <400> 149 64/115 accagaagcc tgt gtcact ctagagataa ctatgaatat gacagcttgc ggaccagctt actgt tcggc gartaaaaatc aaccazgata Lgcaagaaac tgcagagaat gcatagcaac acatgaaaca cctggaactt caggagaatt atczt-agca tgtattatgc tcccctgaga caagaagcac agtgactatg ggaagtagta tagagtt ttg gctattagtg atcaaccaga acagaggacc ctcagggagc tgtcgcatgg aaccgataac atgttggcat cagtagctag tct ttagtgt ctcggatctg ttagtttgtc agtcagacag atgtgatcca atgaaaagct cacctttaca tctggctgtt aggaatcatg at~ttaaarttt cctttcctgg gttataaat t ctgtggacat tggatgtgct gcatagrgctg atttataaaa gaa agcaaag ggagatggta ggtaaagaag ctcgccaaat catgtccatc cttgtactta tttcatagaa gaacacttga gtagtagacg qtttgcagaa tgataagac t ctaatgacgt gaaggcaagc ta <210> 1-50 <21L> 372 212 DNA <213>~ Rat <220> <223> Clone 4,157 (MLSSH) <400> 150 accagttgag tgctcacaag ttggaacaag taazgagatc caacag-agag tgacctatat agtttttggt ataaccatca aataaattct accatggatg tgtattgacc agcttggaaa qaagaaatag ga g:ttattaaa tgattgatgg ggaaagc aga agagaattca gcaaagtcaa gagggaaa tg ctttccaaga tgtatctttt aaggggaaaa gacttatctt gaaaatagac gaccaaacaa aatcaagaca gttctg-ttt agcagtggta qraatcaacaa gct-.ctaagt tggctgccaa accttcaggg ttgaccgtaa ggagtgatga aaccaattat ctgttgatga <210> 151 <211> 529 <212> DNA <213> Rat <220> <223> Clone #158 (MLSSF) <400> 151 acaaagcata cataatgtcgc tttaagcatc cttcatctt tccttagcgc ccgccctg-a ttctccazgt gagtIgaaagt tataaccatc catgttctgg acgtggcatc cctcaggcat 120 tgccgttagt catccttcak agcgtcccct gcagtcattc actttccagt caag-ctggtc 180 65/115 tttgaaattc ctggttg gc atctgagcca cttaaacatt ctgtatagtz agcaaaatgt cctttt-tg ttacattttt tctcttttgt actgctgtct tctcatctac caataaacct tgcttgctgc ccaatcaatc ttcatttgtt ttagtttggc tcagttaatt cttttatgrag tcacctccat tcatttzcat:- tgttttgztct tactcaaccc ttcatatttt ttccaaaaaa ccttgaagct gcacagttgt atctccattc tctcatttt agaaatatct aatcctatta gtgcctatct gaccaag--ta akagactttc zaatgtaaaaa aaaaaaaaa <210> 152 <211> 577 <212> DNA <213> Rat <220> <223> Clone 4159 (MLSSH) <400> 152 acc-aagactg tgacctgtta cgaatttcca tctgtgcttc tgtgttgtzt taacazaggt octataatzic cgcctcctttt atrccacaga cagcaaacaa ttttgcacag ccagcccttg tactctctgC tacagcaagt t aaaa acc ag g tgtgctcay actttgtccc gtttaaacct gaatgtggc t aac aagt ta a gaagcagagc cttaaaac ta attatcgtaa agaatatgat aaacagat Ca ttgggacat-t tctatgatag ggcccygagt gctctggtga acttttgagg agttggttac gtttaactcc tctgagcagt zcttatttat caaaagttac ttttggctca aaataczata ttgacctgag cctcgagz tcctcattgc aagccaatgg acagtccatt ccaccttttt aaaaaaaatt acttat.Eaca tttctacact ttagtatttt tataaacttt ctcaaggccc ggggaagtgt tcctagcatc accatatcag cC Cggtagt C ttt.ttaactg ttcaaaaaCC ttcaaccaaa agaacztaca <21.0> 153 <211> 619 <212> DNA <213> Rat <220> <223> Clone 4160 (MLSSH) <400> 153 actaagcttt gggcttatta aatata=tttg aaataaaac cttagaaatg aaaaagttcc aaatarctagt gazggtaaaa actgggaaca gagaaaatta cagaactaat ctactttC~a ctrtcaaccta Caacagagcc tazcactgtt tggcttatca tcaataatac tcctgataag atcttggtcC aattacacac atatagatta gtagattaca 120 agcagacaga 180 tgtatcctcc 240 aacacacctc aticatctcac attctgttct aagaaagctg ttcctcatga taataatgtt attccataaa actgazgcca aagaagctgt cacaatatgc ct~tcaaaata tgtctatcac aaaatcaca 66/115 gcacaaaaac tttgatcttc agtctgcaac tgaaatccct aatgaacttt ataagattct ttatataata ttaataactt aatcacacat tttcataaag cactaaaata agaatgaatt cattattcaa atccaaatat gccccagtgt tctgtaattt qttgatctct aggtattcat gaataaagag cacattcctc ttataatttt ttctattcag aatatgcatt <210> 154 <211> 191 <212> DNA <213> Rat <220> <223>~ Clone #161 '(MLSSH) <400> 134 acctcatgaa ggctcgacatg atgcccccc tgtaz:tggaa tatgatgcta agaggctact ggggagrgtcc agcctzcttg cgaaagcagt ttcatctggg cctgagzttaa agatggctca 120 gcacttgcrtc tttttgatg atgtctggac caacatcaca acttactgat tgacatgaca 180 gatccacagg a 191 <210> 155- <212> 187 <212> DNA <213> Rat <220> <223> Clone #162 (MLSSH) <400> 155 gaggtaagct ttttttttt~t ttttttttt ttttcgatgc caatcaaaac ttcattatkg ~ttaaacjat acaaaaataq ttaaaaaaag ttacaatcrc ctatatatga atcgcccttt 120 ccaaaattcc cctaaargrr ctgwatgcat ttatctrcgt grgdtaaraa zcktcatact 180 aattctt 187 <210> 156 <211> 206 <212> DNA 67/115 <213>' Rat <220> <223> Clcne #163 (MLTSSH) <400> 156 cgatltggcct gccggcagct tk:kkvacat- 9gtttgca ctagatgcaz tttttttct: agaagtagca ttaaaacaaa gcygsgcgca gtatgatgat actgcratcg cttcgagcgc ttt-ttttag gg-ytagccag ccagcagcgt cacgcattat 120 tcgagcttcc tawwgagaag tgaaragaga t-ctagtcamw 180 tcaaaa 206 <210> 157 <211> 250 <212> DNA <213> Rat <220>' <223> Clone #164 (.-SSH) <400>' 157 gattggtccc wgakca~kcvg cccccgcg acaagcvttt kwwh-acatct tcttvagaac aatwgmcagg aagggccatz zgaatgccca agtgtcgcag gtgatgawvt tcakaatygg cttcgagcgg ttttttttt ttttttttt tttaattaaa ggccacattw 120 cgattwaaaa ccttwyyhcs wrrrhdgcaa twactacaac 180 ghccgwagag craagggaa gcaaggcctt ggagggagca 240 250 <210>' 158 <211> 512 <212:' DNA <213>' Rat <220>' <223>' Clone #165 (NaLSSH) <400:' 158 acaagctztt ttt:ttrt~t tttttttttt tttttctgaa taaagaacaa attttattct aaaaatagat cttagtaaca atgaaazacc aaaattagtc attacaatag aaaaatggca 120 agzctcttctc ctgaagatac aaaattacca caccataaaa tatgttgcca actctcatat 180 ttgaattagt ccttttatgg atttactcac tgttttatct taaaaaaaac aactcattct 240 ctagaaaagc taggaaagt. agcatttgct taagctagac ttggaagaca atttaggctt 300 68/115 aggaaacacg ttcaaac2taa aagtaagaag acaaaraaart tztcaatttt acacattaaa aagaagtctc ctcaacagaa atcctg~gtac 360 caaattagaa agacattacg taaatt-actt tzaaccceaa ctcggtggaa 420 caaataatga ccttgctc-ta agaaagttct :tgtatttcc aaag gc tag 480 attcacgaca atcttggagg gt. 512 <210> 159 <211> 63 <212> DNA <213> Rat <220> <223> Clone #166 (MLSSH) <400> 159 acctaccttt gtttatttgc :attaaactg tttgagaaga acaataaaaa aaaaaaaaaa aa a 63 <210> 160 <211> 252 <212> DNA <213> Rat <220> <223-> Clone #167 (MLSSH) <400> 160 ttzggccctc gctttcgagc ctctgtgca ctcctaagga tagtatgcat ggcgccgggc ttttttttt gavagaacac ga gctcgabcbt cgccagtgtg acggatatc:- gcacaattcg tttttr-z tttttttztc aagaaacaaa t-cttatgaca atagagggca grgcaagacc tgtcgkgagt tgttcacagt <210> <212> <213> <220> <223> Clone 41 (PLSSHfl 69/11S ':400> 161 acacaggatt acatggaggc ag-cgctgg gctttttgct ag-tcagacag gataocgaaca g~actgtcctt coatataccc aatccaccac acttcacocc caataaatgt gagc~catca ttcacacgcc tcactttatt tttccccgta catgaagggt- gtggacggac aaggacactg gaaagacacc zcct9ggtcct Cttccccagt tcattgtctg cctggcaac ttgattetc taggcagtgg agaaggttct cttcctttca aacaatat~c acaaatagtt r-acctg <210> 162 <211l> 187 <:212> DNA <:213> Rat <220> <:223> Clone #2 (PLSS~i) <400> 162 acagaagcaar cacacatggt gtt cggggcc gactbgt at-gcatagtt tggctat ttc t cc t gga gt acaggattg gt-ggattcaa acgaggcaca tagacatgt acatgatgag gc~aatana-gt atagctacac acattggcag 120 cgggggctsa gggctztct ctt-cctgcca ggtggcctgc 180 187 ':210> 163 <211> 131 <:212> DNA <213> Rat <220> <223> Clone #3 (PLSSH) <400> 163 acc:tcgcgt gtctcttcca aatatgggag accctgcaca cctggcaact acggcgaatt tgtccaagtt cc tggctacc catttcctgc ctatgtcgtc tattcaagzc agcacacgat 120 aactgcatgg t 131 <210> 164 <211> 389 <:212> DNA <213> Rat 70/115 <220> <223> Clone #4 (PLSSH) <400> 164 qgcgattggg aacwtcggct tctggcaatg gtbamcyytg ctcgttcagg bgtgv.gatac ccatcacctk cct-ctmvatg ttcgatrcgt aadtgtcact ttczcacacca tgtaatytag cgcccccrntc ggcccsgcbc catgctcgak accgcccgcg ttgccagcztg accttgbagc ycagsgabtc yc gyc cc cac bmt tthtvt ckgccgccag tgcaggtadc tgttcaaagc g-vagcarcaa aktcaggacc gacymcttag tgbtgatgga tctgaaaarg tcccatatcg tagyagcaga sacattgcmt aabcccssaa atctgcacs gggacgtcac aycggatatt cccctaatgt gcagttcct azt tcc caga <210> 165 <211> <212> DNA <213> Rat <220> <223> Clone #5 (PLSSH) <400> 165 acaag~tgtag aaac cccag ggcgcatcct ctcctctgtc agcatgcaac tgagccazga ctgancactc tccaaatatt tggatactgt <210> 166 <211> 350 <212> DNA <213> Rat <220> <223> Clone #6 (PLSSH) <400> 166 acaacatgta aatatagc.at tcgggacctg ctctczgtgc ggtaaagaqt cccagtggcg tatagctgct gtattgcaaa gtgcgcctta tgttttatga c C.cc agc agc 1ttactgaaca gttacagacc tatcctgcgg ctggtttgcc gcaaacaaaa tgt caaaggg tgcaacatta. aagactcatg cctCtctgcct aaagccatcc accaggagua tgcggaactg gcagaggtgg gaagggccac tcaggagggg tcaccagtat tagggtaacc ttgaacatcta gcacttaca. C aggaacCtgc tggctcttgca acttctaaca atgcagtatt gttc :gtgct 71/115 <210> 167 <211l> 169 <212> DNA <223> Ra', <220> <223> Clone #7 (PLSSH) <400> 167 agatatacaa gattgtagaa gtcaaacact gattccctca gc tgcagaaa accztcaaag cagtatctaa tgaggtgcga acagcaaaag aatttataaa atgaatacca gactgccatc agtgagaact atcagacaat 120 ccttacgtcg acagttgcca gtgacacbc 169 <210> 168 <211> 206 <212> DNA <213> Rat <220> <223> Clone #8 (PLSSH) <400> 168 gtacttgggg cctctgagag gggagggctc csygaat tyc gtaatcaaag akctggtacat cctagwttcc cagkcacact acctggtgct ggtggcagcg ctttcagacg gwwaggacgc ttgtvmag-ga ctatayaygg actctctgat gtttgggbct 120 ctctcatgtr acgcchcttc tcaaaacyav gacyctaaag 180 g9gc9g 206 <210> 169 <21:7> 102 <212> DNA <213> Rac <220> <223> Clone #9 (PLSSH) <400> 169 qagcaccatg tgt-tgctgat gaactgagtt caatcccaqg gacccacatg gtgagaggzt agaatggact tgcaagttta agcaacactg tctgtttctg ta 102 72/115 <210> 170 <211> 125 <212> DNA <213> Rat <220> <223> Clone 410 (PLSS4) <400> 170 actaaagaaa ggztgtatz caaccacgia gtaat-atttc aagctactaa aggaatagtt 6C taoctattta gacagcagca atttctacta cactttttat aagctcaaaa cacactaz-gt 120 ataca 125 <210> <211> <212 <213> <220> <223> 171 120 DNA Rat Clone #11 (PLSSH) <400> 171 atattagtgc aczt gagtctg agagttgtgc agtgggtctg cagggcagat acattagtgc agaggtittgc tagggcaggt atattactgc agaggtgtgc actgcatctg tagtgcagga 120 <210> 172 <211> 295 <212> DNA <213> Rat <220> <223> Clone #13 (PLSSH) <400> 172 acaaaaggca atatatgtct tctactgcaa acacgcccat atcctcgcacg atcgacggac ttccactcag ccacaatgct gggcaatcac tcaggggggcc gzgctgazcg cttttgggcc atttcattcc aacaatgaga 120 tcgiaattcga gtctttgata ccagaaccga. ggcctggctc gactgtcctc 180 gctgcmta-ag gggcgcagaa gccattcagc ctttggctac aatggagagc 240 73/115 tgtatatctt tggaggttat aatqcacgqc ygaa-tcgcca zt tccatgac ctctg <210> 173 <21-1> 270 <212> DNA <213> Rat <220> <223> Clone 414 (PLSSH) <400> 173 acgattaaat gcgt-agagaa gaagcatgaa tacatttttg ggatgtatga caccgtgtct caggccactg tccagccatt aaazcagtac cttaycaagc agctttgtct acagacttca cggggccttt cagcgacaca ggtaggctct tytrnaaatca tttgcaccta ctc-aaatc tg gcctccagca cttaggaggc gtctgctgag atgacttgtc attcccaggc atgattttct cttgatagct gaagaccctt tgtgggtac t <210> 174 <211> 88 <212> DNA <213> Rat <220> <223> Clone #15 (PLSSH) <400> 174 caaacagagcc cttatttatt atgtgcacgg ccctaggttc aaccracata cccccaaaga ccaaaaaaat taaacggatg tqtaatct 88 <210> 175 <211> 173 212 DNA <21-3> Rat <220> <223> Clone #16 (PLSSH{) <400> 175 cctyctngtc tgttctnnnt tcctttcctt ttatggtctg ttagttttca cggtgactcg 74/115 gccctaggta tcnbagcgtg cctgggctcg ttcaagcctg ttgcaaccct gagttaagac 120 ccatagggtg ggtc:t-rnat ttz-cccccat tttictztag acttgagcaa aat 173 <210> 176 <211> 227 <212> DNA <213> Rat <220> <223> Clone #17 (PLSSH) <400> 176 acatcttatg gcgagtggcc acccctgaga tattacctca ttatg-cagaa gtaacatacc cttcatgact gtcttgacaa aagcttaaaa ccacatctga tggaagtcca actttcagga 120 accaaggact gccagaaaat atctgcctct acattatqca tgcatctaga cgcttacctg 180 aattctgcct tttataaagg racaaacagt atgaagaagt gaactgt 227 <210> 177 <211> 99 <212> DNA <2'13> Rat <220> <223> Clone #19 (PLSSIH) <400> 177 acaaatgtcc actggggatg ctgtgcgctc caggaatcgt ctcgazgtoa gggtccacca gccggacc cggatagama tactcatcca caqgtgtgt 99 <210> 178 <211> 260 <212> DNA <213> Rat <220> <223> Clone #20 (PLSSH1) <400> 178 acgqwa~ccc tctctgccaa gccatcctgg atgaaaccaa gggagactat gaaaaaaatc 115 ccgtggctc ctgtgtggag gaaactaaac azcccaactg ctctgtaaga rttccgaacad 120 K-vcatctctt agccgttgtt ttcttccta-b tgcraggctz nagtagghaa gttvgcctzg 180 tcag-taagti tymattaacc ttbc:zttgaa taatggtagc ccataaartta tggtttzaga 240 tcattcatct gtacctgccc 260 <210> 179 <211> 981 <212> DNA <213> Rat <220> <223> Clone #21 (PLSSH) INO <400> 179 acaccaacat aztcaatzacc act ttcc taz ctatgaaaaa ttztcctaac agggnaacaa ccc=tccccc cwaaggggag ggggaaaccc c caaatgggt cccaaagggg ttaaangagc cctccctttt agtccccrtt gggmcccccc ctctttt-caa cttcgcccct tattctaata ctgaattgta gaatccgagc tttcctccca aggaattcca aaaacctgcc cccgggggcc tccggattta ccggsggttt tat tt mgc cm gaatgtaggg sccaggctaa qccccctttc ggccCt t Cgg ccttaaggcg gagggaaaaa gkcttnaaaaa aacgccctaa ct--aaccagc atcctaccc ctaacac tag ccctacacat CCgggggggg cgcccccrgc aattzcccct ccccacttaa aggggcgccc accccttttr accttttagg cggggttttc gccctgtttc nttttccccc tttacccccg catcaattgt ttca--aacag cgttttcgat cattctacat aacaga gaaa cgcttcccca aaagcccytc 9gccggcggc ttggccttgc ccgcttaggc g-ggccstttt gccccaggg ccyagaggt t cccnaaaatt tcagccggggn ggggaaac t c at Ccyaggcc aaacactact atgaccaact atgatacatt a -ncc cnnnn gccgggcttc gggggggccc ttttttlaaag agggaaattcc ttttccacca t tcc cggggg gggtcccttt aawtttgggg ttttgggggg tncccccct C ttttttttag cC tatatcat tctatccaca aa:gcacctc tccctgccaa ggggnncaaa ttttcgcgaa aactcggccc ggggggaac C cccctttggc ar-ttgggggc ggtcttgggg cctttttttc gccytttagg gg1ntccaggt ttaaagggga ggagttkgcc <210> <212> <213> <220> <223> Clone #22 (PLSSHi) 76/115 <400> 180 ggcggacktg .Kgcagamktc cttta-tttag tctcttgcta taccaztaac gctgctgtagc cgtcccgtct qgc tz~atggc tagcay-tggc ctacttgaa cctgctgcaa aagaagaaagy aratgcatgc tgtgagzgcQ gcgctcgtc: acattrtgttc gatttgtcac acacaggc ct ccgagckkct aac cgngc tg rnnnnrjnnnnnt aacctctct cgtt ctgc Ct aaaggagcat gccagtrtgc tgtacccaag acgaacgtcg zcdt~tgat gattgctgaa gcatctcagc atgcgaatc gayttggcgg aagaat~gaag tctcaactac actccattzt a <210> 181 <211> 447 <21-2> DNA <213> Rat <220> <223> Clone 423 (PLSSH) <400> 181 agagattaga ccacccagca zcacactccg actatagaag aagtaaataa tgaaaacctt aaaataccac cggaatatag accagcatta tctagagcg gtttgatgaa arcattgagt tgddztggca aagtgacgca agaccgctta aagcagattt agaggccttc gagcaggctc ctcaaga-.ga cgtatgagaa aatcggatgt acaacaaaat agcaccatcg acc-matq tgggagcctt rtggctaaacg caaatcctgc ttaataacgt c--ttgtttta tcgtaccaga caagtgtatg gacrinscaca gtztgcagag catacaaaat cccggcagaa tgctgaggc gaataaaaat cagaatcatg ccatactcc attcttcact gatttcaact ggagaaaatg accccaatgc toccaatag ctggagacgc <210> 182 <211> 192 <212> DNA <213> Rat <220> <223> Clone #25 (PLSSH) <400> 182 acacgar-aat cctgtaacgt gtggtaattc tacaagagtt ggagctgtga aacgcaagty ttccgagaat aatggragtk cagttzctaa acaagcaaaa ctcttgctctg argggaggaa 120 ccatwtgcca tgactggtat agaagaccty tcagggaaaa ctcttcaggk tttcccccag 180 tatqtatcct gt 192 77/115 <210> <211> <212> <213 <220> <223> Clone #27 (PLSSH) INO <400> 183 accqcacacrg aggtggactt ccgggaaggc crgttcgwrtt agg gattgtcaat. tctgcggaak ggaatacctg tcatccagga. gcartggacag ccagrcagcta tgatagcvag ccctggnzcc atgcgggtat caggtgtgat agacacagggt gccagcygtag 120 avgaccttca aggtgkgctt acagbcytck atlggtacgca 180 tgaaagcgtg aaccggagac waggaggttt atgggtaatc 240 243 <210> 184 <211> 162 <212> DNA <213> Rat <220> <223> Clone #29 (PLSSH) <400> 184 acacaagtca tcttaaaaaa -taggggtgtc agcagagttc tatccccaaa ccaggcaggg caataaatgt atganagtga aaacaaaggc ctatctgcag ggcagagctg ttcacgtgag cagggggaat aaaaarcctt 120 caggattctk ggagactcag gt 162 <210> 185 <211> 157 <212> DNA <213> Rat <220> <223> Clone 431 (PLSSH) <400> F-cacagttta cagctacaaa. aacctacttt ggtatttatt acagaaaagt gttcagttaa tcgtattatt ccttcagcaa atattcactg acacaaaatc ctctgcagca ttttacagca 120 78/115 tatgcagcct cgtacaagtt tagazgagtg gatttgc <210> 186 <211> 288 <212> DNA <2-3 Rat <220> <223> Clone *!33 (PLSSH) <400> 186 acaaacgaaa ttcatcttta agtttatat ttttt-gttg gaagcaaatt ctgactttgt atcaataagg ct cczcccat aaaigccgaa gaatagagag ggtgaacttc atgaccagca atagaaactc tcacacctcc actgcaaatt tgggcccaca gccaattaat tcattttatt 120 tccaactttc ttttttctta ccaataaatg aatgaaggca attggaagaaa aaaatttgaa caatataaat ttgatcaaca 240 aaaggaactt aacaaaattt cagtaccg 288 <210> 187 <2 11> 212 <222> DNA <212> Rat <220> <223> Clone #34 <400> 187 acttttlatct I agtcgtctg gaacgcgtgt tccgac~ttc acactgccat ggtccccatc ttatlttattg tcagtctatt cttactggbc cacttttctg tccccccgag taaacggtct, acctgcaagg actgcgcztta ttcatgaaca gaacgacgtg 120 aaatctgaag acttaacagc tggcatttat zgr-aattcat 180 ctgacagaga at 212 <210> <211> <212> <213> <220> <223> Clone 435 (PLSSH) 7 9/115 <4CC> 188 acaaaaattc :cccagcgaa ccttttaat ctctatgaag attagttata tacttcaaaa gtgtaagctg cctgtcactt gtqoagacttg Cgg tgtaagagtt gaaccaaaac ttatatacat tagtctgtgt gttcttgcta cgttatgtga 120 taagactaca agggcagtat gktacctgcc 180 183 <2 10 169 <211> 105 <212> DNA <213> Rat <220> <22-1> Clone #36 (PLSSH) <400> 189 acctcaaagt tggaaggctc agttctggga gtgtccctcc ggtaggtagg tagagtgcct acctagcacg tgtgcctgat tgcctgcact ggggggaaag zaagt 105 190 <22.1> 157 <212> DNA <213> Rat <220> <223> Clone #37 (PLSSH) <400> 190 acagcztcac cagtcggagct acaacaagga tggaggtatg gggatgtgtg gcccctactg tctgacttca actacctaca caccaactgc tttgagatca aagctcccac cagaggaggc gctctacggc ctgcggcaac 120 ancttcctgg agatggt 157 <2710> <22.1> *<212 *<213 <220> <223> Clone #39 (PLSSH) 80/115 <400> 191 ggtactgat ttggatggtg ccattctgtg gaactcggca attgtaagtg acttggagtt 6C tccacccttt tttctcttcgc aagactzggg ctccattcgg tccaactcrtt agggtctaga gtccatctt. cacattcctg tccac~aaat tctccagc azc catttca gattcacaca 180 gtgagtacct gcc 193 <210> 192 <211> 202 <212> DNA Rat <220> <223> Clone #40 (PLSSH) <400> 192 acztancgggc gtgcathcdg gttacttctg- tcatatgtcc gacttgggcc-tctcatgatg catgcatcag agcdcaygca cagtgbtgat ctqcaggaat. tctcgtgcct ttcgacgccg cgtgccgcch cggtgcaggc 120 tgtgcctatr tdtacat tat atatayatat atatgtaata tayatgtayc 190 tcacagaatc ta 202 193 <211-> 225 <212> DNA <21~3> Rat <220> <223> Clone i#41 (PLSSH) <400> 193 accagctgtg cacggcagct tcaact~aaga azacccggtg cccaatcctg tgatcaaccc ctaccagcca gcacttcctt caggttactt atcccacaga ctcagaaccg tctrgcatac tatcctccta gccaaattgc 120 ccaagtcctc gctgactqct cagggtgcca gacctcatcc attccaggaL 180 ctatccaccc agctgctcct agaccaccat ttagt 225 <210> 194 <211> <212> DNA <213> Rat 81/115 <223> Clone #42 (PLSSH) <400> 194 acggtgcagt acacctttcc accacctgtg cacgcatcta aacattacac gggaz-agata gggkaattta aagtcaggat acataggata c tagtc t tgt aattagcaac g aagagaaga atgggaatgg tgtttttctt atcataagta ggaaattaag aagataggat agatagatta gtctaagzt: agagagcat c gtctgcaga attgttttc ttttgtkttt ttttgggctg aagttaggat atgttaggat catag acaggtatcc ccgzccgaga atcatgctac ttgtttcaga ggagggac tg aagttaggat aagttaggat zttggacat gacccgacca atattcagct gttttgctgt ctatagtcaa ttaagtaazc aagttaggat aagat aggat cccgcatccc gzcazaaagg ggacagggaa tgagttgtca ttaagaatag ataggtgggt aagttaggat aaggtagatc <210> 195 <211> 180 <212> DNA <2-13> Rat <220> <223> Clone #43 (PLSSH) <400> 195 actgcatzatt ataacctggt ctctagggga tgccaacttc atatatctg aggkrnnsgc tccgtgacag gtgggaagtg gatcgknnnt ggctczgaag natczkbaga ccaaggagat cgtacccccc acacaataca 120 tggtgtgcag cagcaggctg gztaccbnat acctgcccgg 180 <210> 196 182 <2 12> DNA <213> Rat <220> <223> Clone #44 (PLSSH) <400> 196 accacattgc acgtqgcttc Ctctggatat atctaaaccc ctCtgCaCat ctacacttag atggagttgg :-caaagggaa catctgggtt atgcccttttt tacagtagct ttagagaaccg 120 tcggcatgtt gctgttgaag tgtggagttg tgagcgtgga ctatggacag tzcgacagcgt 180 qt 182 82/115 <210> 197 <211> 198 2-2 DNA <213> Rat <220> <223> Clone 446 (PLSSHi) <400> 197 accgaaacca ctgggaatgc cagtcagttc cagttcataga atagcatgtt tctgagattc tccctgttct tcccctcagk ttaatccctt yttcatgttc tctccacyga ggtgagaacc atggctctaa agaagctca gccaccagcc cctgattgyt ggagttct- cccatgtt ctgt ggagag 120 agkttccttg 180 198 <210> 198 <211> 256 <212> DNA Rat <220> <223> Clone #48 ',PLSSH) <400> 198 acttaarcgg cacatasfaa cttctcaaac ggctttggca ctcctttqgt cttccttgct .cccgctcct tcagagzccg ggagcgggct acctgc cgtccagatt ttgctcgagg agccacagtg tcatct-aagn ctcccttggg tttcttgctt atagcacctt thga-natcgc 120 agctgtcaga aaaagatggc ttcctcttgc gactcgttctt 180 tttr-ggagac atgagcattc aaggctgaat ctgractcggt 240 256 <210> 199 <211> 448 <212> DNA <213> Rat <220> <223> Clone #49 (PLSSH) <400> 199 83 /115 acaatctcaa gaagaaccta gagtgrtt-c caztgcttca aactcaaac cagacatttg atcatgctgg gcz gccact ttctatcaat attggctatt cagtcttact gtttacctca tgcagagggc ccactcccgc tgtgagttca gactatttgg ttgqrccttta gattcttgtt ttgaaatggt gacctccatc cragaaatg aagcaaatga tagctcgcag cagtgtgt aaaatcacca cactgggaat gcattztgtgt ctatccttca gtcatcatct ttg-gagaagt aagacatccc aaagaattat cagaaagctt ttctgattta zgcatttt-t gcagccccgg taaccacctc tgacactgga ca2.attaaaa gtcaatcact ctttatgaaa aacccatttg catatacacg agtcaagaag ttgttctgaa <210> 200 <22.1> 241 <212> DNA <21.3> Rat <220> <223> Clone #50 (PLSSH) <400> 200 acccacgcca tcggtcttggt tttgctaagt tgataccagg gttcatagca ttcaatqggt tgatgggaga ttgatcaata actcr-actgt tttgagaata agactgacaa g-cataatctc gctg-Tccaat gaccaagggg catatacatc cctgaccccc 120 gaacttcgtg ctagtataatg ttt-cagctac cagaaaaaa-g 180 ttcaatataa taacctcttg gtaaataata ctgccactag 240 241 <22.0> 201 <211> 222 <212> DNA <213> Rat <220>' <223> Clone #51 (PLSSH) <400> 201 acactgac-gc ctcagtctgc cctccagaca gccactgagS atgaccgcgc tggcgaacgt ccacctgcgc aaaggagcag gtgtccccca caccgacgac ctccacagta aagtttccgga 120 agadgtctat gakytccagg gcccgtgggc gtaggcagaa cataaaaatg aggggcgtaa 180 caatgggact cagcaactcc tccaagatga acactgcctt at 222 <210> 202 84/115 <211> 104 <212> DNA <213> Rat <220> <223> Clone #t52 (PLSSH) <400> 202 actgacgaat agcaaagaag agaccctaac catggccttc cgtggtgagc cagcacaggg gagaatatcc tggaggatct gaccaaagcc atcattgagg atgt 104 <210> 203 149 <212> DNA <213> Rat <22 0> <223> Clcone #54 (PLSSH) <400> 203 acagzttgtt caaggaattt ttgttgaaaa atatgatcct acqatagaag attctzaztag aaaccaagtt gaagtagatg cacaacagtg tatgcttgan atcctggata ctgcaggahc 120 ggagcag-tt acagccatga gagatyTgz 149 <210> 204 <211> 255 <212> DNA <213> Rat <220> <223> Clone #57 (PLSSH) <400> 204 acagtaagrac acacacccac acacgaaccg tatgtttccg cataagtatg aacaatatgt tttcaacg ataacaaaca gttaaaattt czataggagt taaaacaatg ccccattatt 120 taaaaactgg ctcagtaagt ct-aaattcaa gatgcagctz tgtcaggcot ctctaaacca 180 gatgacggaa acgcagggaa gacaggggca gggctctgac :-agcagttac aactggcagga 240 aqggatgaag acaat 255 85/115 <210> 205 16C <212> DNA <213> Rat <220> <223> Clone #59 (PLSSH) <400> 205 ggzcacacca caagtaaagt ctgaagtagg acagraaaacg ctccgaaggc t-cgttttggzc 120 acccgltatz attaaaaatg gcagacccct aacaatatgt 160 <210> 206 <211> 115 <212> DNA <213> Rat <220> <223> Clone 460 (PLSSH) <400> 206 acacttagtg taattgcaac actccaacag gaatcaaatc gaaccag-cag aaccgtttct gcatctatara cttccatgta acacacat gcacacacct ctatgacttc catgt 115 <210> 207 <211l> 243 <212> DNA <213> Rat <220> <223> Clone 461 (PLSSH) <400> 207 actcataaat acaagcagct tgacattgqc attaacaatm wtaan-attag acatgtct tacacatgca ogtctcggcgt ggaactcaga acttagccctg ccaagatagg rgagcttatg 120 crt::tcgtcg aagtgtgtgt gtgrgtgtgt gtgtgtgtgt gtgtca:aaa cagcccacag 180 tagaatacga tgactactct cattcttgtg attaaagctg ccctz~ctaca cactaatct 240 tgt 243 86/115 <210> 208 <211> 2.35 <212> DNA <213>, Rat <220> <223> Clone #62 (PLSSH4) <400> 208 acctcagctC accagtcrgga gtgctatcct cgagagactt atccctcaga gagtcatgga ccaacgcaag ctcagcaggg ggaccggatc cacggtgtggc acgcagaaca czgagggatg ctcaaggaca 1.20 cgagt 135 <210> 209 <22.1> 285 <212> DNA <213> Rat <220> <223> Clone #63 (PLSSH-) <400> 209 acttcatcag tc tatgaagc gcCagawcgcc tggaagcctt n sggcc t C caagcgcc agccaacaag taaccttgct tgacgacczg gaaagccgaa aaaagcaggc accacctgca agatgatgtc cgggtagacc tgggtgacag ccgtgggcaa agaccggcca ttcatggggg 120 gacctggcag tgtatggtat gctgcgagtg atggagggtc 180 atgcgacact cacacatcca gccttggtac ctgkcccggg 240 ttccaqCaca ctg~gcggccg ttact 285 <210> 210 <22.1> 265 <212> DNA <22.3> Rat <220> <223> Clone #65 (PLSSH) <400> 210 acaCtatgag aactacagam gcagaaaact agcagcagtg acctacaatg gagtagataa canrcaacaac aaaaggcaac ttaccaagag ccctctggcg cagatggagg agaagagaag 120 87/115 ggaq-cacgtg gccaagacga agwwbazgga gatgaaatg gagcagagtgt ttgagatgaa 180 gqtcaaggaa aaagttcaaa agctgaagga ctctgaagcc gagctccagc ggcgccatga 240 gcaaatqaaa aaaaattta=g aa-.ca 265 <210> 211 <211> 347 <21-2> DNA <213> Rat <220> <223> "lone 1-66 (PLSSH) <400> 211 actaatggca ttttctgaacg tgcagattag atgtggac ct ccggttttac acccaactcc tggcacgtgt tcgcccatcc ggtcactgct tgtgactctg tggtggqttt aataaattct cacatgcagt ctttgatgcr. ctctgcgtct ggattagaag tcccttaatt taacctcggt ccatgtggga gaaggcagtg tccagztct ccaaaazatt ctgtttcact agg tgcaggt ttctacatcra actgagtgag catctgtgga aagaagggac ctgtgtzatc ttcccagtta cctt-tgaagc ttagaaaagt atattcatta tttacatagt aatcagt <210> 212 <211> 906 <212> DNA <213> Rat <220> <222-> Clone #67 (PLSSH) <400> 212 acccaag-gac gaacaatc tcaactacta tccgttttgc agtctcccat tacctgtcga taacctacca taatttgttt ra:cacagta ggggccgtcg ttggggcttt tcttgctact ccattaaccc tgctgtgcaa tgccaaacac agaagaatcz. tg-tttaagt tttttttaaa cccgcctccg =gcatgca-c tttaaagcac accttgaaac tgctgcaaga gaagaaagag agtttgagca taatggtgaa agt ttagtg ggr-ttttaaa aacaagcc c t agaqgggc c tgggcatcgt atttgttcaa tttgtcaccg gcaggcctaa gtaggacata gtttctcttc aatttttttt gtgttgacta taagccgaat aattcgccec cttgaagata CC tctCt t c ttctgcctga gggagcatgc acartggtttt caccagcgtt ctcattggta tgccttcaga ctgcagatat aaagggac gaacgtcgaa tgrtttgattc ttactgagac gtctcagcac tatttcagtt. atc t ctr ttt atggtcttgg aattctgttg catcaaactg agatacaatc aotggccgco gttttaaacg cc7qgrctcag gaaaccttgc gttacccact taatcgcctt 660 88/115 ca gaaaaccc cctttgccaa ttggggaaaa cgaaacgccc gmccartagc cttcccaaaa '-gggcgctg gatagagaat ggggsccctt aagggggtta accsscgggg ttqqggaac 780 ccgggmccgr aaaattaag gcttaacgcc ccgttwagtg ttccaccctt ttccaaattc 840 ccggtccccc gaaagaaaa: "-gggccytaa ggcgccttaa agrgtttaggc ktscccaaaa 900 atwtta 906 <210> 213 <211> 84 <212> DNA <z213 >Rat <223> Clone #68 (PLSS14) <400> 213 cctcgtgcat gwccwcwwca aggcccagca tctccagcag tggggagaac gagz-ctgctc agagcaccgc aagcacggtg cagt 84 <210> 214 <211> 96 <212> DNA <213> Rat <220> <223> Clone #70 (PLSSH) <400> 214 aacaggtcct agctaagcca gagaaagcag ggaaacaaac tggcatctgc acaccgtctt caagtaaaca gagtccctga cgcacccgrga gagtgt 96 <210,> 215 <211> 164 <212> DNA- <213> Rat <220> <223> Clone #71 (PLSSH) <400> 215 89/115 acaactctta tgctaaaaag cccttggagg gaagtgatca tacagggaarg ttatcaocgt gtagaaaaaa actccacaaa ctgggaagat taaccccgaa tgcttgaatg gataggtgtg 120 ccctcaaacc agctaca-tta tcacccccac ccagccagaa atgt 164 <210> 216 <211> 127 <212> DNA <213> Rat <220> <223> Clone 1"72 (PLSSH) <400> 216 actttagttt ac tgtagtaa cagaacit tataggccct cacaagtgtt aattctcctg taagtttctc tacatgagcc tgtgcttaga tcttagac at agtctttatc ataacaatat taactagcac 120 127 <210> 217 <211> 317 <212> DNA <213> Rat <220> <223> Clone u"75 (PLSSH) <400> 217 acggtgatgg aggacctccc tctgaagcag agcagcgatc agcctctgcc tgcttagc-tt gaacaactcc tgagagttta attctatqtt aatattttac atgtagaaaa aaaaacccta gcaagattgc atcttattta aagtttattt aatgcaggt ttcttaattt caaggttaaa ggtttccaga tcccctcagg aggcaatt-,t scccggc catccaatgc tgcctggatg tacctattta tttcccccaa agtgqttdatt gaatctactt ctaagtttaa ccaatcctta gaattgtatt aatatttcag <210O> <211> <212> <21-3> <220> 218 DNA Rat 90/115 <223> Clone #76 (PLSSH) <400> 228 acctooatgce acaqgcccgc accctgtdtg gcctaoracga gagcaaggcc caactgtcag cgacagtgct cactctactc atcaaacagt <210> 219 <211> 229 <212> DNA <213> Rat <220> <223> Clone #77 (PLSSH) <400> 219 actcaagacc cataattgao tgctgacacc ccctgctgat aaagcacata atgct aatgt agggctcaga ggggaaatac acttctcctg gaaatgt gga gtccttzcaa gaaaatgtaa taaacataat catcg-tagcc aaggaaaaag gcccctattc gctcttzctt ttatgcwgta atttgctggt cttcaaattg gatcactgta gtaaattatc cntgctgrgt <210> 220 <211> 83 <212> DNA 2 12> Rat <22 0> <223> Clone #78 (PLSSH-) <400> 220 gacagcaacc aagaatggat tct-lagcatc gaaggggggt ttctggttcc cgtagctctt cagacggccc atctcacccg tgt 83 <210> <211> <212> <213> <220> <223> Clone #79 (PLSSH) 91/115 <400> 221. :-tcgctc.rgcg tcagtgtcta agtctgatct :ztccagtctg gatctttgag cacagaacz-g gacctcgtcc ccagaaacac ttctgcctct aazcgagtc tctcgatcat cttctcctgc aattctgtat tatcaagtaa gctgtatgga atggaggatt tcoaccacg tgtccaccac 120 tcctcctggg cgtcitcctgc cgtczcac-a 180 atgacat 217 <2210> 222 <211> 172 22> DNA <213> Rat <220> <223> Clone #80 (PLSSH) <400> 222 gaaacagtat cattctgctt gagggtaatg gtgggtgtma taatactcta -gaccacg~c catccagtgg gagcatttgc caaaacttct aaaattgata tagaaaggttg tatcaaagtt cttaaagatc aacctcctaa tagtgtagaa ggtcttctca atgctctcag gt <210> 223 <211> 94 DNA <213> Rat <220> <223> Clone #81 (PLSSH) <400> 223 ttaa aar-ggc actganattg tcggaaactt gactcgccgt tatcaaagag gcaagadagc agctactata agaggtgccz cctgcaccgg gagt 94 <210> <211> <212> <213> <220> <223> Clone 482 (PLSSH) 92/115 <400> 224 acaacacagz- taatttaaac atttcattt ataaatttat gagggattma aataacagaa attaaatatt agttttcaaa aaaaatccac cttzttctcag tagagacctc aatgcaatgc aaa tac tcaca tgaaaaagcg gcagtagaaa taggcagrttt tgccatgcag gagaagcaat 120 atttgaaaat attotagtctca agtcacagaa 180 gtaattagct accttagatg gcctgttttg 240 243 <210> 225 <211> 126 <212> DNA <213> Rat <220> <223> Clone #83 (PLSSH) <400> 225 actgctgcag tcgaagcgcg gtcycatctc gcttctccag aaccogcaca aagctccaga. gcgga!tcczc cacctccggc tccacgacgg acggtattcc cgctcctcgg cggacgatat 120 z cc agc 126 <210> 226 269 <212> DNA <213> Rat <220> <223> Clone 485 (PL-SSH) <400> 226 actgtccaga cgccttgtat gaaatgatgc taaaatgctg gcaccocaaa gcagaaatgc gcccatcgtt ttctgaactg gtctccagga tatcctcaat cttctccact ttcattagcg 120 agcactatqt ccatagtgaac gctacttata tgantgtaaa atgtgttgct ccatatcctt 180 cuctgttgcc atcccaagac aacattgacg gcgaacgaac acatgacgga taagaggccc 240 gccagccccc ttctaagaaa cagtacctg 269 <210> 227 :-48 <212> DNA 93/115 Rat <220> <223> Clone 487 (PLSSH) <400> 227 actgtggttc aaagaaaagg atgctggttc ttgctgggcc :gcatagccc ttgtgagggg cacggacgca ccagtgcct ggacgatcac atcaacatca z-ccaccctgt tgtcggtgca gaagtgcatc gactgcggca 120 gcaatgac 148 <210> 228 <211> 179 <212> DNA <213> Rat <220> <223> Clone #88 (PLSSH) <400> 228 acaggattta. 9ggaaaacaaa gccg-tccgc tactataaca actttcatct ctgcttcacc tacttgatta agattttgaa aatagtttaa acaggaagat agagactaaa ttggaacaga aacagtctgt taaggagccg cagcttaggg aggtz-aagtc tcacattccca ccactqagt <210> 229 <211> 288 <212> DNA <213- Rat <220> <223> Clane #90 (PLSSH) <400> 229 tccagaagcc tcgacattag atttggzgac acgatccctc tctcrctttg ggtcccctgt ccccgactcc cattaacaa-t agctacttcc cacacctcrgg acaccttgaa gtccgacgac 120 ttctcacact gggaatagct cccttgttct tatggaatcc acctgccaac cacccatcca 180 cggactcatc catccttcca tccgtcatcc atccatccqt ccgtccgtcc gtcctgaytt 240 cccagtgcc actgtctggc taggcaytac ccactatcaa. cctggttc 288 <210> 230 94 /115 <211> 221 <212> DNA <213> Rat <220 <223> Clone k9l (PLSSH) <400> 230 acctttggtg gaagcaagca tcctcctcca tcagtttcca gcttgggatc agtbacaggg gcaatgacag caaaaaaaga aaagagcaaa ggtcattaltg aggttacg g agtaatgac gagtggagta tccttggcct canacangtc ccgactgtct 120 cgggactaaa cttggcatcc agcttcctga ggtagaaata 180 gtagtgggcc ttcatgcatg t 221 <210> 231 <211> 89 <212> DNA <213> Rat <220> <223> Clone 993 (PLSSH) <400> 231 actattattt atatnagccg hnmattgzaa agaggcagga aagctctcccg gctttgcgga tcacaaataa cttagtttgt gccgtaggt 89 <210> 232 <21:1> 320 <212> DNA <213> Rat <220> <223> Clone #94 (PLSS-) <4,10> 232 ac cggaagaa cgagczgtct akczctgggc gcacaaccct agaagccaag cccagccatc gcagctggcg aacagctccc tgcacatgac caggaccctt ctaagtgcca cccaaadagg tgaaggggat ggaacagttc gtgaagaaat ataagagrtga gtgggcgacg tgaagcctcc ttccgagatg aa:gctcaag gtgacaaggt gccggagaca gaaacacccc agcagcacgtg qgztccaagg acaagtctgc aagacccaat at!tcctgtta ctgctgcaaa a=acaccatga gggaaggagc tatgcr-gaaa 95/115 <210> 233 <211> 252 <212> DNA <213> Rat <220> <223> Clone #93 (PLSSH) <430> 233 act tatacgt acgcagtgca agt gggatct t gtact tgga gggttccctg cgtcatccaa caacgcagcc actatctaac aaac tggaat qt gccgcaaagc ccaagtatta ctttgcctgg acattggcag ggcttcgggt tcagtggcat agatgcggat gggaattc tt 120 ctgaacatct ggaagatcga gac--gccacg agtttcaaaa 180 attcagacat ctacatggct gaaatgtgtg tgctatgagc 240 252 234 <211> 296 <212> DNA <213> Rat <220> <223> Clone #96 (PLSSH) <400> 234 ac:gzttttt Itccaca--ctt ttcaattagc gtcttcactg atctgctgtg tcaaatctta accagaagac tttaaaaacc gacggagaagta atggaagcat gcagatcaatt tcagtattat catctcacaa ggtttcaaag ttgtgagat~t cttcaat.tta cr-ttaattta gggacccttc 120 tgtaagattg gtcataagaa aatataaaat gaattgacat 180 gacaaaatgt tgcaggtctc attgtcacca ctgtcattta 240 gacctatatc ttaatgtagc cacattgaca ctggac 296 <210> <211> <212> <21-3> <220> <223> 235 134 DNA Rat Clone #98 (PLSSH) 96 /115 <400> 225 accatgagag tctggcttgc gagcctgttc ctctgcgcct tggtggcgca ctctqaaggt ggcaatgaac tggagctzc t.atgaacca aactgtggct gtcagaacgg aggagtatgt 120 gtggtccrtac aagt 134 <210> 226 <211>~ 856 <212> DNA <213> Rat INO <220> <223> Clone #99 (PLSSH) <400> 236 yc Cc t Ccvt a ggcttacgag ctgcgtatga cawctrgack taccaacgrca gscgttggta ccagcacsat tgggacctgg tttacacgtt cttagttgatt gtncccttta tcaacccgga tgggaaaaac gaccgt -aga cccgaaaagg taccacaaca cgkggtgcgc aaacgagt ta ccgcaattcg gtgatckgga acagggtaat kaatcacgtq tatcactatc ggacggttta tacggaagtt aagcttgttt aaacgdatzt aacggttccg caatttaaaa g-tc aaatacaatc gaggrcggta ctggagatak ccctatagtg aagrccaat actgggaarc cctagtagcg agcgcccatg cmcn tga aag cgacsczaaa gc ccc tt ccc tacccggcat gaaatzwtcc gttttaacck cagcaacaac cttcckcaaa ccgatcacac ag tcg-.at ga cgt'tmccaac ccgcaccgtt csgattaagg gtacgggccg tcgaawaacg acgtcaatac ataarrtcac ngtttcattt gatttaagra tggt tacgga mngcagygtg tcattagcwg gtgkcrrccg caattcactg tzgaatcgct agcccttcca aggggggnc t ggggtccttt gggawacatc cacaktaaag aaaagat tt at tcggt agg ccggattcgg ctggaattcc cacragtgtg cwcgagcakg gctgtcggtt Lgcagtcact tcagtzacg g:gcgtacag cgcttcttgt agggttctga sccctgtkac tnggtttggt cggtttgsca gtztataaag aaggaaaaac <210> 237 <211> 272 <212> DNA <213-> Rat <220> <223> Clone #100 (PLSSH) <400> 22-7 acctgtttct agcgggcaogt gttttCgtct cctt-g'titgct agattcctct cagatatccc 9 7/ 115 ggaaccwtcc agggcccaaa cagtatgacg tctgcctttg gagaactaca tcaacctcaaa ctgttgcagt aataacttct g~atggcwgaa tgatcgcagg aaccctgaaa. agttttgrcc 180 acaccattaa cttgattctg gatgarakcy acgwgcgggt gttcagctct tctcagggag 240 tagaaz-aagt ggtatwtggg gtgtatgcca tt 272 <210> 238 871 <212> DNA <213> Rat <220> <223> Clone #101 (PLSSH) <400> 238 cc-agcgccyc tarcttagcg aatcggtgac twcttganag aggtccacng tayt-tytgag ynyt caagc t ctg-wctycag ccccagrccw ccarcataca ccgtcgtz-tt cagtaaatcc cccgaaaagt ccgcgttttc ttggcttt-t ggc ccc ct tt cggtcctctt aa tggnc cc t czttgggctt aaaaggaggc rccygcrgkc ggggcattcc cagcgctaag t ctagagggc rnccacttcgt ccctttcagc tgcgcctttg ctgttaagcc acctctcttt agggtcccyt gcccatcscc tttcaactg ggcnaaat-aa caaccccccc aaaaaactgc atgcckgacc scgggattct ccaattcgcc gactgggaaa aacttgggga aagtgcgaat ccgkaccgct ttcgcaagtt ttaggsctta ggratcaacgg gaaacccaac cccctaaaaa aaaggtggac tkkattttat a~ntgggctta kcagatatcc ctctagtcga accctggcgn ataaccgaaa kgactccccc acaaatt-aca cgccggtttg aggccctccg ttttcccctt cacctngggt ttytCccsgt C gccatttgaw acgcccacgt ttttacactg gtcgcttaca yaccctactt agcccgggac r-gtat~tgccg agccccttac cccgtcaact tcccaaaagt taagtccaag ttcttngctt ttcaaattg ggycgaakgc 120 cggcactgcc 180 ggggccagct 240 attcactagg 300 aaacgccttt 360 agaltagccct 420 rttaaaccgg 480 ggacgctccc tt~taaatcgg 600 ctttttggga 660 cccggtttaa 720 aagygttttc 780 gccaggtcct 840

87. <210> 239 <211> 96 <212> DNA <213> Rat <220> <223> Clone 4102 (PLSSH-) <400> 239 actgtggcct tcccaggatg aaggacatca atgaccatct gtdtcctctg argcagacgg 98/115 tttgtvatgq acttcctggt ccggatggtt accatg <210> 240 <211> 109 <212> DNA <213> Rat <220> <223> Clone 4103 (rLSSH) <400> 240 tczttagagm gcttcattgt cgacgtgtgc ttataa-ccca gzggtcagtc atggbatgcc ccctgggtca ggccatcggc cttcnivangg ctatettcca caagthcct 109 <210> 241 <211> 282 <212> DNA <213> Rat <220> <223> Clone #104 (PLSSH) <400> 241 acccagggaa tgcacgattt gacacaaagg ccgtgtatgc attaaaataa ttataactca ccaatgttac ctgtcttctt tttcatacat agcct Ct ttc tgctgatgtc accttaatgc cataccztga ctcagttgtt cagatggata ctctcttgtc- ctacctctga gcttgctata 120 tgcctgtgca cgcgcatccc tgggtatttt ttaatgtctt. 180 aactatgcac tataaatatt aaatggAtga cttatatgat 240 actttaacaa aaaaaaaaan cc 282 <210> 242 <211> 165 <212> DNA <213> Rat <220> <223> Clone #110 (PLSSH) <400> 242 accttgttga tctcatcctc atacttattc ttgangtcct ccaccaggcc ctgchtgttg 99/115 ccaagctcca cctccagct: cagcttctcc tggcccaggg cttccag-ctg ccgacggagg 120 ttgttgatlgt hacccttcaa acacgtttg ccakgttgcc cctyg 165 <210> 243 <211> 21C <212> DNA <213> Rat <220> <223> Clone 4111 (PLSSH) <400> 243 acatattgtt aggggtcagc catttttaat gataacgggt gaccaaacca gccttcagag cg-t tzctgt cctacttcag actttacttgr tagtgtcfacc atgctcarta tactctcaaa 120 ggacranaaaa aaccttgtaa aaaaaacaaa aacaacaaca. aaaaaaaaca atcttattct 180 gagcactcca gtaacttttt ttgtgtatut 210 <210> 244 <211> 170 <212> DNA <213> Rat <22 0> <223> Clone #112 (PLSSH) <400> 244 acgcaccaag aaagagcatc gaaagcctg ggctcgaac ctcaacggtt ttcatgtgga. ggaagccaag atcctcaggc tcagtggaaa acctcagaac gcsccagraag gctaccagaa 120 cacattgana gtttttgtac aaacwwttbn nnngagctcg gtaycaaggt 170 <210> <211> <212> <213> <220> <223 245 504 DNA Rat Clone #1.13 (PLSSH) <400> 245 100/115 acccgaattc ccaat-tcacc ggaaancccg aaaamr-anag ccccaaancg gnccagcncn g-nnccncagn caaaacattn gatngagaan cc cc a ankn c cnazaaggga gngttagcca gpnccgnac cg gccariL-aanc ggcntttsnc tccgaflaagn nccaagaagg gcgggrlgcaa catcaccctg tcggannaaa cntaatcgnc aacgccncc ocinggcnna ctnincccgt-c ntnagccgn cagggntaaa naaa qgcggccgct ntcaagggcg ttncaaacan caaaagttaa ganggtanc g cccaanntna. ccaagaaanm aaag-,icnggc acag-natgca acgtwtacaa cccccctttr accpggatnc ggggacggcn nggtnccgan nag-nnnnaaa aacagaagnc tttasagggc cgcgtgacng ccagntgggc c-.naaggc aaaagtgcca o caaaanlg ggAnflaggc accr-accnna <210> 246 <211> 234 <212> DNA <213> Rat <'220> <223> Clone #11.4 (PLSSH) <400> 246 acaggccgag catttcccgg tccagctgcc acagcagctg gctctcaatg ggcaggtcca cagtqctggt cttcactttt gccttctttg cttgaggtgg ttggtccatc tittcttatctt 120 tzgazccagc ctgagaggtc cccatctcc. caaactccgc cttgttttct gctggwgtct 180 gtggCtgrttg ctcttcagta tgtggttzctt cctggtccac ctgcatcttc ttga. 234 <210> 247 <211> 149 <212> DNA <213> Rat <220> <223> Clone #115 (PLSSH) <400> 247 accccg~atac aggtgatgat gatgggcaac atcaaagtgg cagctctcct gcrctcctat- ggcacagat-t cgaactgcga ggaccccacc accctctccc gaccggzgca cgacgcaacg 120 cgggagggct tcctagacac tctggtagt 149 <210> 248 <211> 78 101/115 <212> DNA <213> Rat <220> <223> Clone #116 (PLSSH) <400> 248 acgttcgacca tctttgcagc agaagtgtct gcvatgaaaa cgagaaraccg gcagcagcga tccccgcctc aaccgcac 78 249 <211> 389 <212> DNA <213> Rat <220> <223> Clone #117 (PLSSH) <400> 249 accgagatcac abtctgctgg ccacagaaca tgaccaactc ygcaaaabtt agagtctatt caacgagtcc cgaccaatct ccacatr-cta ctatgacatg qtgatt c tag gagaaactca. qttaacgac: acaaacaccc gggggcgctg tatgccaaag tttgaagtat acatcaagca aaccactgna ttgcctacat gcgtcctgt gctgcctgcg aggatgcaac gctttgagag tggagtagag ggtggagcta gaagaagcgg cacccacctc taaagggaag o aaggbc cas gcgaaawa tt ogggotcg gaagakgaa aagaccacag tt--gccttta g-gcggatacc atgaagagat asgacctttc tgagggacac <210> 250 <211> 217 <212> DNA <213> Rat <220> <223> Clone #119 (PLSSH) <400> 250 acaaatt-tat atgactaaga gtaattctaa actcttgaaa. aactacagzt atygatattt tagtbaatat ctaatattta tacacaatt:- tctcaatgat ttcttttatc attgacatca. 120 tttataacct gctataattt aatagtcgta aacacytatg ctaatcactt ggcactgcat 180 gtagtttbss sscataaaag tctactttta tacacgt 217 102/ 115 <210> 251. <211> 187 <212> DNA <213> Rat <220> <223> Clon'e 4120 (PLSSH) <400> 251 tttacagacg cgga tg:ttcc acattatczc gaacac C tctcctgcac ccaagtcgag ctctcacaat actaagctct cagtg-tacta cggagttcag tgcagaatct gtctcttcat ctatt-tcccc gtataaccca. ataccacttg ttctactcct aagttctgct aatgactlgct 120 gagaagagct 180 181 <210> 252 <211> 270 <212> DNA <21.3> Rat <220> <223> Clone #121 (PLSSH) <400> 252 gatctctttc tcgtgacttc Uaaggaacat ctatacccat agattggcaa cttttgcggc tgaccgaagc tcgaaaggac agcggtccaa catcgctgga. rtgcagccgc caaaatgaag ttcaatccct aagaaccgca. aacggcattt caatgcacca. tctcaca-tc 120 ccgctttcca aagaaczgacr acagawktat aatgttcggt 180 gacgaagttc aggttgttcg aggacactac aaaa~gccagc 240 qtgtacctag 270 <210> 253 <211> 81 <212> DNA <213> Rat <220> <223> Clone #122 (PLSSH) <400> 253 103/ 115 acctgttg~c atcacctggt gtccaaactat gcaccgccag cctccaatgc cccaqgtatcc tcctccacag ccaccaccgc c 81 <210> 254 <211> 167 <212> DNA <213> Rat <220> <223> Clone #125 (PLSS-) <400> 254 cagagaaata gcaagtagat tttgtatgct ttgttttccg gagragctztct ggcaaaatgc aagtagatga cttagaccct gtttgaaaag aaatcatgag aaatcagaag gcacttaggt 120 cgtattctag gtataacaag tattccggtc acacagaata acaagtt 167 <210> 255 <211> 106 DNA <213> Rat <220> <223> Clone 4126 (PLSSH) <400> 255 gcaaccgtca gaaactgaaa qcctcagtcg caaccgggcc tcgctcctca acttagcaaa aatgcccaca gatgcatcga gtccctgatt gcwgtttzcc agaagt 106 <210> 256 <211> 222 <212> DNA <213> Rat <220> <2231> Clone #127 (PLSSH) <400> 256 cgztgggg atccatgaag tatgagrtgag gaactggtag tgaattcaat attggccaag ctccatgctgt qtgctcagaa g-tctctttac caaagaccag gagcaggag-c taagcatgtc 120 104 /115 cagtcctcct cttgtgcaac ctttgacagt agtctggtcc acgoggctgc tcagawaagc 180 gctgctcttg tatgtctcac tggtattaga aawtttwcct gt 222 <210> 257 <211> 218 <212> DNA <213> Rat <220> <223> Clone #128 (PLSSH) <400> 257 cggtactcga g~ca?--gactcc ccaggactcc tgcctgcttc aagactcgct gtcacccccg agtcagcaat acccacacct cagctccaga grcagaagcag cgctcaec-ec-,gagcacctca 1-20 aabcctgcct ctczaggcctg ctgagatggt aagcatgagg acacaggaac t--gaaagggc 1-80 cacccactcc tgacaaaacc-aaagttgtac ctgcccgg 218 <210> 258 <211> 245 <212> DNA <213> Rat, <220> <223> Clone *129 (PLSSH) <400> 258 acatagacaa aaaatctatgt cctcagtaaa attcttaaac ag tza aggtaaagag aaacaaccga aaaagacaga gctattgcct aagagaaaga. aatgtgtata cgcattccac agaaatatat acagggaaaa cttccagaaa 120 ccaagccaca c-"tacaaaaa ggaaagctga attttat--tt atcaacagcc 2-80 atgaacatyc atacgtaata atctacg-cac aca tcacagt ttttaacgtt 240 245 <211> <21-2> <2 1-3> <220> <223> Clone #131 (PLSSH) 105/115 <400> 259 accataagca kzttccatgg qgtcagagaa cggcta-gaka gt: ctggaaa ccakaggwgg tattgttttg gagatcagga Cctcwccgzg tagccctggc ctcaaactc 109 <210> 260 :64 212 DNA <2:i3> Rat <220> <223> Clone #132 (PLSSH) 260 gggtgcttcc ggagcatggc ccrt cgt tgtg agttggacgg gccctcagct atgaatgttc caaatgaata tctcgttc:g tc-ttcca-ga ttcaggcacc cccgttcctg qgtagaggcg ttcagttcg-a 120 aacaagcctc cagcctttct acgttctgtgc tacg 164 <210> 261 211 108 <212 DNA <213> Rat <220> <2231> Clone #133 (PLSSH) <400> 262. actgcagcat tccgcagata catgttg-gam aqtmgcttgg mggctgcaca cacggagatgq cgttccccat gtmtagcctg cvttccttgg ccaacagcct ctcccact 108 <210O> <221> <212> <21-3> <220> <223> 262 745 DNA Rat Clone #135 (PLSSH) <400> 262 106/115 acatg~tgat:- ctttcaagc ttaacgqaat gatcacggaa gatacggcca accagcatgt gataggtgaga tcagaactga acagtcgttg ccctaagcga cccaaagggg taaacgctga gaaaggaatg cgcactagaa tgaggtgctt cat caaga tg gcctttctat ggtcacqtct cczgtgctcg ggttttaaga cttagatccg atgagaaccg wtctgcaaaa gcgataaaat gaaacccntt acgccct-agg tgtqaaggca cgtgttgcag gagtttgaag actgcaccta tccttcCttc tatcagcttc cttaaaacgg cat sc got ta cccagggtca tcatcaaact aac tggcgcg gcaggggaaa gctaa cactcacaag agaaccagtc atggtgaagt aaagtctggc tctzcttcct tttgtaagac gggccatcaa tgc ctcagaa attgaggcaa ggggcgcccg tttaaacgcg tcagtctgag gacttgctgc ttcatagggt ttccttcata cttctctccc aatcggcagc cttacaattg rggc tgaaga aaagtacggc gatgatctaa gactggaaac agagcacttc tccttgaaaa gcagcaagag aagtgcccgg tctgtatgaa ctctgtttga gcagtcacga tccatagcat tcggracaag gggccatcg cgggtwccaa caaagtggcc agraaggccg acraggcttc <210> 263 153 <212> DNA <213> Rat <220> <223> Clone #136 (PLSSH) <400> 263 acacagataa gaacccacct aag tcagtt~c ctacaggct-g ctgctaatgr .gcacccctt gctggccggg gggctaaccc aacgttccac ccggagcaca tgcatgttca gtaacgccac tgagaatact gcattgttag 120 gacagctgct aga 153 <210> 264 <21.1> 288 <212> DNA <213> Rat <220> <223> Clone #137 (PLSSH) <400> 264 acgaaaaaag caagt-cactg ttggtcatczt aaactcrcctt acataaaaat attccctgca ctgaaaaaaa atacatgtaa acatctcctc gagaaccctt gasssygtcc attatgzctt cccaatgtcc cacaattctc 120 tttctctgtg ggtatcagtc tgcctzcttc tttacagaat ttggactctg 180 t.qaqqctggc gtggtttgac tggcaggaga aggatgatca gcacacatag 240 107/ 115 gazgtgcaag aaaaagaaca tgaacttata taaactgaa gttggctc <210> 265 <211> 100 <212> DNA <213> Rat 288 <220> <223> Clone #139 (PLSSH) <400> 265 accattggcc ctgcttcccg atctgtggag atactgaagg agatgattaa gtctgggatg aatgtggctco ggctgaattc ctctcatqgd acccatgagt 100 <210> 266 <211> 136 <212> DNA <213> Rat <220> <223> Clone #140 (PLSSH) <400> 266 gcggtacctt c--gctgcatt agtatccaca tccatacaat tagatcagac aggaagtcaa taagacacaac gaaacagggc tcatagccgc t-atttagggc tgcagtggtt tcatgtggat ttacccactc agccgt <210> 267 <211> 183 <212> DNA <213> Rat <220> <223> Clone #141 (PLSSH) <400> 267 accgccagtc agggttcttg atgtgctct. taataaaggg aaggacazgt ggtacaatgt. caccttcaca gcaggtagac aggaacatga grgcacacccc agctgctttg caagggttcc 120 agtcatcatc gtcatcgttt tcat-cctgtz tagttagtgt ctgtgttwag atgggcacca 180 108/115 2 10> 268 268 <2 DNA <213 -,Rat <220> <223> Clone #145 (PLSSH) <400> 268 acataagt-aa actaaatggc ggrttctgtga zatccagtaa ctcgcatacc ctggtgtgtg cgatgttctg caatatcccc gt-tattttgc ttg'ttcgatt tgcacaagca tattgctctt tttatctttt cctt.ttaa. ttttggttac atcagatgga gacagtctgg ggacagttct 120 ctrtctccact agtggcatgc tcagtt&&Cg-t--cswatctctc 180 tctcattgtt ttaacaaaag gantcbaaca acacaaaacc 240 agagaatt. 268 <210> 269 <211> 175 <212> DNA <213> Rat <220> <223> Clone #147 (PLSSH) <400> 269 ctuaaatat atcrgcatttt atgaacactt ttgtatagcc g cacaacgica laaatcgtca ttcagctItg tt.ttaagata accgct-tact tgtgctttaa tgicttaatat gatggaaagt. ttcltgftttt cgtttctaaa 120 gagcaz cagt taaagacata tgtttgacat tttaa 175 <210> 270 <211> <212> <213> <220> <223> Clone #151 (PLSSH) <400> 270 109/115 gctatggaqa aggga9cagt ataaggggtg tt-ctgtagga acagaaccgg cgacttatca cttaaggctt cctgactgta ttttcagatz tcagacaact tggctgt 107 <22.0> 271. <211> 348 <22.2> DNA c213> Rat <220> Clone #152 (PLSSH)

272. awgcmtgaca rnkaagrngtgg r nnm-innnns tgggctgtcy gtaaatatty tttccctttt tctcttgcrg tcmagktcgg gtgtccctct tgt cagaggt ngagctttgg tctactaatg rcgaccacat cctgatacat tgagaacaag gataaaaaat catgcctcgt atgcccaaat cwcactgaca taatcagcat gtctgqtaga raacccctct ctctttcttt aaccaaaaaa gtgccgcwcn aztcaggcwt taccattacn aytggccnint tctgcacttg qtcagcagcc tcaagatgqt ctacttcogct cacactga <210> 272 193 <212> DNA <213> Rat <220> <223> Clone 4154 (PLSSH) <400> 272 acacgtttg tgtttcttag aggtttaaaa tggcatgctt tgcatgcaaa ggaaagccat tgcaattagt ctttkattat acctgtatct tgggttttat aaactgctgg cttgagtttt 120 gttgctctta aaccacagta cctgkcccgg gngggccgct cgaaaaccgh attccagcac 1.80 actggcggcc ctt 193 <210O> <21.1> <213> <220> 110/115 <223> Clone #163 (PLSSH) <400> 273 aci~gtggagg Lgcttcaaag gcaggataca cggcaatctc tqgcacattt ctattgttga tgzacttktd gcagttccaa acacaatl.,a ttaggtaagc czaadddtg atgaatacca 120 caaaaaacac aagt 134 <210> 274 <211> 250 <212> DNA <213> Rat <220> <223> Clone 4169 (PLSSH) <400> 274 act tcccaca caciggggaca tgtgcttttg gcattcatgc caccgggaat cttcatttta tgcaaaaaca tatggaaaca atgttgccag ttatgaaaaa cctaatgcac aaagaaggat attatttttt gattgcattt atcatcatcc acttgUgatat cattttataa tatazaattt aatagtataa ganaacatat ttttgtttcc attaacactg at att cac tg <210> 275 <211> 315 <212> DNA <213> Rat <220> <223> Clone #170 (PLSSH) <400> 275 acaagcwttt bwgtaaatca acrttagtga aagtgtttgg cagaggwcag cg-gtgtcttg tttttttttc tttttttttt ttttaagtca ttgtatcttt aataaccggg aaacatggaa aaaagtcgtt ccttttacgg gttgatgccc atcaccacag gtgagaagggg attccaaaca. gcataggaag gcttccaggc tcacgggatg ttgctgataa tcagccgggg gacgagcaac acaagagatt aaca~rgccct gtcgcggztk ctg-ggtcatg accaccztga agcgtttcrtt gatggtg~tt agtat <210> 276 111/115 <211> 1.38 <212> DNA <213> Rat <220> <223> Clone #171 (PLSSH) <400> 276 gtacacttct tccagcgggg tgccgtaatc gggtggccaa agaatcagaa taagtgttga taaagaattg ggtctccacc tcgmagaaag tacgtatttmn atttcagtct gtaaggn~gta tagtgatacc 2.20 a tgg tc at 138 <210> 277 <211> 173 <212> DNA <213> Rat <220> <223> Clone #1'76 (PLSSH) <400> 277 gggcotctag cgkgctttcg cstc-rgtcttt atgcatgczc gagcggccgc cactg-ytgca tggcatatct gccwgcacct cagcggtccg cccgcgagca gtgtacggta acacaggttt acttgtcaca 120 agttcctcag aatttcaatt tzggagatta ktgccgtgta ava 173 <2.70> 278 <211> 120 <c212> DNA <213> Rat <220> <223> Clone #179 (PLSSH) <400> 278 ggcatt:aac atgcagatgc tccctaagag gaagcagcca gtacgncgnc tcagagcgag cgagtacgac agtacctgcc ctggtgcggc cgctcrincag accqaatzcc gagcacaccg <210> 279 <211> 190 112/115 <212> DNA <213> Rat <220> <223> Clone #181 (PLSSH) <400> 279 acatttgcca gctcagtcca tgcttgctga cagactgagz- gggcagatcg tctagaagca tccacatctg atacttcaga atcagctcat gcagcacatg cctggcacct tttgccrgtgg acaatggagg ggcctgactc gtcatactcc 120 ctggaaggtg gacagtgagg ccgggatgga accgccaatc 160 190 <210> 280 <211> 174 <212> DNA <2113> Rat <220> <223> Clone #185 (PLSSH) <400> 280 acaagchttt ttaictctct atgggaacac t tyt tt ttyy agaagaagca atcaaatgga ttyycttttt tztttttttg acgtaaaata gaaacagact gatatccatg gctgggacag cagcttcagc aacagaggcg 12C cacaggggag gaacaggcat caaacwg-gac aagt 174 <210> 281 <211> 153 <212> DNA <21-3> Rat <220> <223> Clone #192 (PLSSH) <400> 281 tacatqtctg agcaatggat tgzgcaagct gatatcttag gtccaacaga ctgaactagt crttgttgaaca agggttccca ggtttgtctg tctgattctt ccacatttac aggaatcaca tttgggcgcg 120 atgctg-tagc tagttcagg. acc 153 <210> 282 113/115 <211> 160 <212> DNA <213> Rat <220> <223> Clone #196 (PLSsii) <400> 282 aztgtgsycc ctgtcaaga tatctrztata zctakatgca catttcgtgc ctgtatqtgt tgtctcgwag cggccgtcct avtgctgtat gcgtatgatc ctttcaggtg ctgtgtzgsc tgtcagraaa gtgtg-ycgrg 120 tttctaggtt ataacatatt 160 <210> 283 <21-1> 177 <21-2> DNA <213> Rat <220> <223> Clone #200 (PLSSH) <400> 283 cgggcgaazt tcyg.c cacag atacactcta gggccctcha mttcggtctt, kagggar-akgg gatgcatgct cgagckngbc accaatgctg rnayggcmtca tcgcagcggs ccg-cccagg ccagggtacz ccccacacaa 120 mghkatctg gtg-ytgccag cag-yczagct ggcctac 17 <210> 284 <211> 197 <212> DNA <213> Rat <220> <223> Clone #201 (PLSSH) <400> 284 acttgggaag ggcuaaggtat ctttg~tccat tcgacttgga caaztcctag gccaggtaat caggtcrgcaa ccggagaaaa ggggacgcca ggctgtctgt sctcttccag cctagcaagc 120 ag-ac--gcgta gcgtctgtgv ccatctggna ggtggggtgg tctctgaggc gacagctgcac 180 gctzgacggg tggdkta 197 114/115 <210> 285 <211> 183 <212> D)NA <2 123> Rat <220> <223> Clone #206 (PLSSF) INO <400> 285 ctgagcagga gacggtctaa tctgctcaca 9cg ttaccatggc aacaacacat catcagtagg gtgaggctaa cctgtctcac aacccagctc acgttcccta ttagtgggtg aacatctaac gcttggtgat 120 atgataggaa gagcgacatc gaag-gatcaa agcgacgtcc gtatgagcct 180 183 <210> 286 <211> 205 <212> DNA <213> Rat <220> <223> Clone #207 (PLSSH) <400> 286 agct.cggtac caaacttggc gtaatcatgg tcatagctgt ttcctgtgtg anatt-gtntc cgctcabaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc tggggt~gcct 120 aatgagtgag ctaactcaca ttaattgcbt tgcgctcact gcccgctttc cagtcaggaa 180 acctgzcgt-g ccagctgcat tantg 205 <210> 287 <211> 219 <212> DNA <213> Rat <22 0> <2231> Clone #209 (PLSSH) <400> 287 gsssbbbnnt tttttttttt tttttttttt tttttttt tggctttgaa acttagctta ttcaaagttg tgaacaacgt caagaacacr tttgggctac ttaattacta ttttaaggat 120 ggsgkgcnga ttcatagagt cagcattatg gttttcgggg ggagtataaa gattctgcct 180 115/115 ctactttycy tttacagtaa= aactgtgaca aattwattg <210> 288 <212> 243 <212> DNA <213> Rat <220> <223> Clone 4210 (PLSSH) <400> 288 acagtgtgga ctagaagaaa tgcctctgra caaztgatac agt gaggctgtcg aagtattgtg tgatgtgst t caatggaatg gttcctt atg tgccacaggt gacagatgaa gatcgcctt't gatactgtat ctattcaggt ggatatttta tccaacagtg 120 agcaacactg aagaaatcac ttctgaagca ctagaaaaag 180 gaagaacagg aaaaggaaaa gagacgtctt gtgatagaga 240 243 <210> 289 <211> 105 <212> DNA <213> Rat <220> <223> Clone #222 (PLSSH) <400> 289 cgtgtacgcg cgagtggaag cgcgctgctc gagtcaggta acggtagttc gtatcgtgta tgtatcqcta. cttcttgcgc agacctattg gatataggtc aacta. 105