WO2007066794A1 - Animal non humain a inactivation du gene brak - Google Patents

Animal non humain a inactivation du gene brak Download PDF

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Publication number
WO2007066794A1
WO2007066794A1 PCT/JP2006/324622 JP2006324622W WO2007066794A1 WO 2007066794 A1 WO2007066794 A1 WO 2007066794A1 JP 2006324622 W JP2006324622 W JP 2006324622W WO 2007066794 A1 WO2007066794 A1 WO 2007066794A1
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Prior art keywords
brak
human animal
mice
human
mouse
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PCT/JP2006/324622
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English (en)
Japanese (ja)
Inventor
Takahiko Hara
Noriko Nara
Yuki Terasawa
Chouji Taya
Hiroshi Shitara
Rie Ishii
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Tokyo Metropolitan Organization For Medical Research
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Publication of WO2007066794A1 publication Critical patent/WO2007066794A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276—Knock-out vertebrates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out

Definitions

  • This book relates to knockout objects in which the BRA gene has been destroyed, the BRA attack skunk method using this, and the B antass operation method.
  • mice that destroyed T or its body the instinct due to obesity was improved (ys T e a ⁇ , a e Vo 389 p ⁇ 60 614 997).
  • BRA Beas ad Noe exp essed Che oe
  • BRA Beas ad Noe exp essed Che oe
  • Cain genes have been found to be colored in dairy color bodies. These chis are composed of 92 to 99 amino acids (8,000 to 0000), each with 4 stay-fitting stays. This is a characteristic of this stadium tomb and its 25-sided anomaly.
  • Cain is classified into C, XC, and CX CC 4 groups based on this characteristic (Z ok A e ⁇ , y Vo 2, ⁇ 2 27 2000). Therefore, XC chi has been classified into 6 types so far, and by the absence of G e 9 (ER) in, E R + XC Kai ER CXC Cain. Belongs to CXC Cain that does not have an ER sequence, and is named CXC 4 because of its name.
  • B has an activity of being specifically activated by B and prostaglandin E (K e a Ex ed Vo 94 85586 200).
  • B is the sphere and the pre-differentiated
  • B is a key that has a property not before the T cell and B, but before the organizational charge (K e ⁇ ⁇ Ex ed ⁇ , vo 94, ⁇ 85586 200). , No other known XC Y with the same spectrum.
  • the problem that Ming solves is to clarify the sexuality and K of white spheres and kufa, and to analyze the lamellar state of obesity-induced lesions of BA genes. To provide the qualified items. In addition, it is to provide a method for squeezing BR antass and B antass using this material.
  • Examples of humans include those that are in the state of becoming obese when they are in the state of obesity and those in which the number of cases of being in the state of becoming obese are reduced.
  • examples of the above-mentioned article include an article, and examples of the article include a us.
  • a B-attack song that is described in E () is used as a control substance, and a substance other than a substance is treated as a substance, and the substance and the substance are put into a state. And a step of administering a quality to the animal, and a step of evaluating the animal and the condition of the animal.
  • A is a diagram related to the establishment of the BRA knockout system. The construction of the targeting vector and the UBSBRA locus after homologous recombination
  • the position is shown schematically.
  • the box () indicates the BRA gene's Xon component.
  • P P2 is the position of the PCR ply used for ES cells.
  • B is a diagram showing the establishment of the BRA knockout system.
  • C is a diagram showing the establishment of the B knockout system.
  • Ta RA was extracted from Us (), Us (), Us (), Lung and (), and tested for BR RA by Northern Butty. ac is the amount of RA on the surface.
  • 2A is a diagram of the shape of a geneus. Each of the wild (), (), and () male parts of the wild was identified.
  • 2B is a diagram of the shape of a geneus. The weight of the genius Uss was raised for 14 days.
  • 2C is a diagram of a generous shape. Shows that the geneus is usually grown in 6 or 5). The graph shows the mean and quasi-error of. 2D is a diagram of the shape of a geneus. Indicates that the geneus is usually raised in 6 or 5). The graph shows the mean error.
  • 2E is a diagram of the shape of a geneus. Indicates the weight of the device when the geneus is normally grown at 6 or (5). The graph shows the mean quasi-error of.
  • Figure 2 shows the shape of the geneus. Shows a a ac (ac ”) separated from the enclosure of a normal genera (usage of 6 or 5) of the gene. The graph shows the mean quasi-error.
  • Figure 3 is a diagram of Us's. Line pieces of A C) D woven weave woven from A B or C D were prepared, and 480 bodies were used as primary bodies for coloring. The brown CIGNA indicates the location of F480 sex cells.
  • Fig. 4B is a diagram related to the ins test of the geneus.
  • Fig. 4C is a diagram of a grape of Geneus (with a gusset). The mice grown in (RD) or (D 6) were allowed to stand overnight and then exposed to glucose. The (g) of grapes was determined. Rarely littered with
  • 5A is a diagram for the gene Ushomon.
  • Muss which are genes grown in (6, or 5), were collected, and the abundance of the wass was measured by ESA.
  • the graph shows the mean error of the group.
  • 5B is a diagram of the gene's hom.
  • 5C is a diagram of the gene's hom.
  • the genes grown in 6) or 5) were collected, and the amount of adipectin was determined by E.
  • the graph shows the mean quasi-error of.
  • 5D is a diagram about the homo of Geneus.
  • 5E is a diagram of the gene's hom.
  • the degree of susceptibility raised in (), () and 6 () 5 was determined by a quantitative kit.
  • the graph shows the mean quasi-error of.
  • Figure 5 is a diagram of the Geneus homo.
  • the freeness of the mice grown in ()), 6) 5 was determined by a quantitative kit.
  • the graph shows the mean quasi-error of 6A is a plot of the current R A.
  • the present state of BRA mR A in Us's vessel was analyzed by Nozza Butti.
  • the ap is the amount of RA that depends on.
  • 6B is a diagram of the derivation of B VI RA in obese mice.
  • FIG. 7B is a diagram related to an insult test of a geneus.
  • Tg represents the Langusius.
  • Fig. 7C is a diagram related to the ins test of the geneus.
  • FIG. 7D is a diagram showing that BRA partially damages Insigna.
  • the derived C2C 2 cells were intensified at the above-mentioned size, and the insemination of A Se 73 was determined by the standard. Good for carrying out Ming
  • BRA was shown to be a novel mediator of inducing obesity-induced insulin.
  • the BRA gusset is fully installed due to the weaving of the activated cushion.
  • Ming's lawn was born according to Mende's law, and if this is the case, it is possible to obtain the same litter of the present subject (that is, () () 's). There is a result that can be done.
  • non-human foods such as mousse, rat, peach, rabbit, pig, dog, nes, sheep, etc. can be mentioned. Soy sauce is preferred, and more preferred is mousse.
  • Akira Hit shows the instinct when he is obese. Also, when you become obese,
  • the number of classes is reduced.
  • gene analysis using the tissue of obesity suggests that there is a large amount of white-induced trafficking in obesity-related diseases.
  • the loss of BR which has sex with Akira and Kufa, was significantly reduced, resulting in a significant reduction in the number of guages in the obese state, which resulted in no indication of insufficiency in the fully-fed state.
  • the weight of obesity is higher than that when normal foods are fed to animals of the same gene by feeding high weights to chickens. 8 or more, and more preferably 2 or more).
  • a state-us can be obtained, for example, by allowing D2 (Quar) to have a premium of 2 for a female of 6 and above, but is not limited thereto.
  • BRA knockout (BRA)
  • a gene fragment is obtained from the Us gene library by a method such as PCR, and the B gene (or a part thereof) is masked using this gene fragment. Then, using the DA technique, all of the skewed B gene is replaced with, for example, an isine gene, and then 5 is treated with, for example, a theaxin (DT) gene and a theta A fragment.
  • DTA Gene Introduce the gene of simple swaze sanse (SV k) gene to fabricate a targeting vector. After (targeting) the prepared targeting vector, it is introduced into the ES cell by using the composition () and the homologous assembly is prepared. From the homologues selected, ES cells that show resistance to antibiotics such as G4 8 Shikubi (GA C) are selected. Here, it is preferable to confirm by Southern method, such as the selected S target object.
  • the ES cell described above is returned to a pseudo-parental mouse, which is a mouse embryo of a mousse, and a dichotomy.
  • a pseudo-parental mouse which is a mouse embryo of a mousse, and a dichotomy.
  • a combined mouse B-us
  • a BRA knockout B-us
  • a BRA knockauus and a lumbus usus usususus
  • a method in which DA is separated from the spleen of the spleen and confirmed by Southern examples include the method of isolating RA from the mouse brain and the like and confirming it by zambul, or confirming the expression of BRA in us by stub.
  • a meal is taken and swallowed, and this mouse is fed for a predetermined period of time. Then shoot a shot. Then, it is confirmed that when the blood glucose is monitored over time, the blood glucose level is significantly lower than that of the control mouse (or littermate).
  • the BRA knockouts obtained were used to make them obese.
  • BRA antagonism was administered to animals other than the clear ones (the ones that did not lose the function of expressing BRA (hi)) by administering the quality of the I will try.
  • the candidate traits have similar characteristics to those of the present invention, it means that the sex of BR is suppressed regardless of the expression of BR. Therefore, it can be determined that it is the administered B-state.
  • it includes a BR method squeezing method using the above-mentioned Ming hee (hi) and hee (hi) other than ming's stuff.
  • the BR status means a substance that binds to BR receptors in spheres and crofa and inhibits the sex of BRA, but by itself does not exert the W effect.
  • the feature of the screen is, in particular, that it includes the steps () to (). Note that in the step (1), the order does not matter, and the shift may be performed first or at the same time. . 0 Humans and the process of putting the humans in the state (process) Administering quality to the humans)
  • the animal As the animal, the animal of the same kind as the control animal, which has the same BR gene and whose BR gene has not been destroyed (the animal whose BR gene function has not been lost in color), is used. It is possible to use either wild type and / or BRA, or both. Hi, Akira no Hi (BR hee) It is preferable that they are littermates.
  • the weight of the animal is higher than that in the case where the normal gene is taken by the chicken of the same gene by making the chicken take the high fee.
  • a female in a state of 6 can be obtained by allowing a female of 6 above to obtain a premium of 2 such as D32 (qua), but is not limited thereto.
  • slaughtered animals and slaughtered animals are put into the form, it is preferable that they are the same as those in the feed.
  • Examples of candidates (for B anthase) to be administered to humans include various kinds of artificially synthesized naturally, tanks (including body), quats, and organic compounds.
  • Examples of comparative evaluations in the process include, for example, a small number selected from the number of in-plants, white courage, and adipotinity. By comparing these evaluation targets with the control and the prepared ones, the BRA statement can be easily squeezed.
  • control specimens and specimens (below, each specimen) are allowed to stabilize for a predetermined amount (for example, 6 of Us), and then the specimen is irradiated with an insulin solution. Then, the control and control animals are compared with those for which blood glucose tagging is desired over time. If this is not significant at this time, it can be evaluated as the desired BR anthrax after administration. If the test subject remained significantly higher, B-assessment can be evaluated.
  • a weave of cotton is sampled and finely cut. After dissociating the fragmented tissue with various elements,
  • test subject had a significantly large number of constants, it can be evaluated by the target B VI ass after administration.
  • the knowledge in 2. above can be applied to the knowledge of the chair.
  • you can use for example, Us Adipokti E SA Kit (Otsuka Pharmaceutical Co., Ltd.). Compare adipose and cutin to a certain adipo and cutin. If there is no significant difference, administer it.
  • the target BRA antase can be evaluated.If the test substance has a significantly lower concentration, it can be evaluated by the target B antase administered.
  • the squeaking method may include other steps in addition to the above, and is not limited. How to determine the effect of BRA ant
  • the BRA anthase obtained from the above-mentioned screening shows excellent quality, it cannot be said to be useful if it has an adverse effect on the treated animal. Is. Except for the fact that Akira no Hi and the gene are defective, it is possible to remain unchanged in the wild and show no abnormal properties over the long term after birth. Therefore, when BR antus was administered to babies other than Akira's chickens and BR was in a non-functioning state as in Akira's chickens, the state of administration was compared to that of Akira's chickens. Suru At this time, if the test subject is found to have no effect (effect) on the control subject, it can be determined that BR antus has side effects related to the condition. Actions include, for example, survival and weight gain, hematopoietic activity, and effects of performance, and these can be used to determine the effects.
  • the BR anthase is as described in the above, and is preferably obtained by the Sung method of the above ().
  • the defining method is characterized by including the step ()).
  • the process of comparing the human with the human () The process is explained below.
  • test subject who administers B-assay is obese, but not limited thereto.
  • the same explanation as in step (1) of the Skug method in () can be applied.
  • BR Anthus can be taken orally and is not limited to and can be used in accordance with applicable law and regulations.
  • the BRA assay may be administered in a pharmaceutically obtained hydrated state, or may be administered in a pharmaceutically obtained hydrate state without limitation.
  • Examples of comparative evaluation in the process include survival and weight gain, hematopoietic activity, and a small number selected based on performance.
  • the side effect of BRA antus can be easily assayed for the type and mode of action.
  • test animals show no symptoms after administration of B-anthus and are tested for weight gain in the same manner as the control animals. Note that if the weight is lighter than that of the control and wild animals, weight gain will occur.
  • the method tests that the test animals are still within the absolute range of the absolute (blood cells, neutrophils and phenotype) rates in the blood after administration of B-anthas. Although the number of in vivo uterine craps is lower than that of the test animals, it is possible to make a comparison with the above-mentioned animals effectively because no difference in the bone marrow cells is observed.
  • the loss of the function of expressing BRA of Ming is devoid of the ability for the tissue profile. Therefore, as a result, it has characteristics such as a decrease in the number of white courage. Therefore, we will try to administer BRA mediators by administering quality to them using Akira no Hi (Hee). In the same manner as in the non-human animals (i), the administered animals showed signs of increase in the number of craps for the insulin, regardless of whether BR was expressed. The effect of BR is similar.
  • the BRA medium means a substance having a specific migratory property to spheres and coufer, and a substance having the same property as BR.
  • the features of the skip specifically, include the following steps (1) to (). Note that the steps (1) and () do not matter in the order, and the shift can be performed first or at the same time.
  • an animal of the same kind as the tested animal, in which the BA gene has not been destroyed (animal in which the BR gene function has not been lost in the color body), can be used.
  • the BA gene function has not been lost in the color body
  • Hi, Akira no Hi (BRA Hide) It is preferable that they are littermates.
  • the weight is -2 or more (more preferably -5 or more, more preferably -8 or more) as compared with the case where the normal gene is taken by the chicken of the same gene by making the chicken take the high fee. , And more preferably 2 or more).
  • a state mus can be obtained, for example, by allowing a female mus on 6 to obtain a high price such as D32 (Claire) for 2, but is not limited thereto.
  • slaughtered animals and slaughtered animals are put into a condition, it is preferable that the same thing be done for feed.
  • Candidates (for BRA media) to be administered to humans include various artificially synthesized substances, tanks (including body), poqua, and organic compounds. It is possible to go and is not limited, and even if there is a gap, it is possible to adopt the public law and regulations. Also, it can be determined in consideration of the kind and condition of the test subject and the quality. Examples of comparative evaluations in the process include a small number selected from the number of isps, the number of white phages, and the degree of adiponectin. By comparing these evaluation targets with the test and target test specimens that were put into a state, the BIV media can be easily masked. The method of comparative evaluation is illustrated below.
  • a test substance and a control substance (below, each substance) is allowed to stabilize at a predetermined level (for example, 6 for a mouse), and then an insult solution is irradiated. Then, the test specimen and the control specimen are compared with each other for blood glucose monitoring over time. If it is not significant at this time, it can be evaluated that it is the target drug administered. If the test subject remains significantly lower, it can be evaluated as having been administered and not of the desired quality.
  • the weave of the fish is sampled and thinned. Then, after understanding each element of the fragmented tissue and understanding, only the curve is recognized. Measure the number of phages using a facet or a sorter, and compare it with the test specimen and the control specimen. If this is not significant, it can be evaluated as the desired BRA mediator after administration. On the other hand, when the constant was significantly decreased in the test animals, it can be evaluated that the dose was not the target quality. As for the knowledge, the explanation in section 2 can be similarly applied.
  • Sculling method which may include other processes in addition to the above.
  • the other steps include various steps that can be carried out in the method of screening a desired material using a knockout machine or the like. Below, the implementation will be described in more detail, but the present invention is not limited thereto.
  • the genome sequence () of the us BRA gene was obtained from the us sequence (accession: AC 65347), which is available from the book data (www cb hgov).
  • the base sequence of the B gene is the base sequence (7902 b) consisting of bases 72 78 to 18079 of the base sequence of the color body.
  • Heating for 95g at 95C ⁇ : 95C (60sec) Ag 57C (60sec) ⁇ : 72C (60sec) is cycled for 40 seconds. .
  • the oga piece was prepared by PCR using the genome D A of C57B 6 us as a template and the following ply and Ta pomerase Takara) under the following conditions and conditions. Prino
  • the temperature was kept at 7 ° C and cooled at 4C.
  • Chimeric mice were obtained by microimplanting the selected ES cells into R-us seedlings and transplanting them into CR-us mothers. By mating two BR genes born in the C57B 6 Usu sister,
  • the tail pieces were processed overnight at 56 C in DA ff s C p 75 300 mm C 05 o P40 oe ase (0 g) 50. This was heated at 98C for 20 minutes, and then it was placed in 4 temps. Type) and Taq Pomerase Takara) were used to perform PCR with the following composition and conditions. Privacy
  • the high-molecular-weight genomic DA RA was extracted by (It was put on the ybo desa. For the idea, a 32 dCTP sensitive probe was used, and the radiation signature was detected on the B3000 (Fim).
  • R2 ply 0 is 0 5 1
  • mice were exposed to 6 shots of either Insane (commercial company) (075 g) or Grape (commercial company) 075 mgg. Targeted by Test R (Academic Research Institute) after hours. FD32 (Quar) was used for rearing, and it was carried out for 6 or more females over 6 hours. 4. E SA blood quality
  • FCS FCS Us gG (g) 0 g in PBS was allowed to do 30 on ottin a (70 BD fus) g). Twenty volumes of 5 CS PBS was added, and the mixture was allowed to stand on TC Spavidi (BD phenyl) 0) water for 30 in 5 CSPBS. 20 quantity of 5. Add CS PBS, PBS containing Po de (g) was suspended in 2 g and the cell density was measured by ACS BD.
  • the wall weave was set with 4 homemade PBS and then lined. 6) to Ochin 480 (B 8,
  • Sp-avid (BD fagin) identified with horseradish oxidase in PBS (10 g at room temperature for 30) and then developed with dianochrome to develop color.
  • the BRA () and the litter of the same were given to induce the experiment.
  • the () us group continued to gain weight, but the average () () us group was always 20 higher than the (2B2C) () us group. Since the weight gain () was changed (), it is presumed that it was not due to weight and appetite.
  • the weaving weeds were used to compare the percentage of weaves per body weight, and there was no significant difference between the () uss and the control uss. Look at the () uss
  • White weave fat in uss causes abnormalities in individual knots.
  • blood glucose was usually () Uus, but in the raised group, it was elevated (4A) o In () Usus, blood glucose was elevated as compared to normal blood glucose.
  • the number of () us that was growing normally was reduced to 49 of () () us (5A).
  • the values increased 2 ⁇ 7 in the () () us group and 98 times in the () us group, respectively.
  • the expression of BR mRA in the us was analyzed.
  • BRARA was synthesized in brain, lung, and bone marrow (6A).
  • Ming it was shown that BRA mRA was also expressed in the uterus, white tissue, and tissue in addition to them (6A).
  • the BRA RA of the () us weaves grown was about 5 times increased (6B).
  • the T mR A level also increased. Therefore, the BRA is considered to be a member of the Adipokai gene that is fully transcribed.
  • adipectin acts on liver muscle to enhance calcification through sexualization of PPA (Ya ac T ea ⁇ , a ed Vo18 8, p 288 295 2002) Ya ac et al. Administer adipontin to genetic Aus. Reported that the obesity was not improved but the amount was improved (Ya ac T e ⁇ a ed Vo 7 94 946 2,000) o BRA () It is presumed that the reason why the above-mentioned state did not occur was due to the use of adipotectin. It shows that the usability of the weaving that has been proposed so far and the profitability of the issuance are supported, and that the organizational capacity via BRA is essential for the issuance. Obesity models reported so far (experimental
  • BR is a molecule discovered in the expressed XC chi, and it is clear that B knockout is also useful in the investigation of the immune system of cancer. If the B knockout is sold, it is thought that researchers around the world who are interested in the life and cancer of the drug will obtain it and upgrade it to the theoretical function of BRA. It is expected that this uss will be accompanied by the exhibition of research.
  • the cD A base sequence (12) report containing SBR A was obtained from (S ee a Ae amo Vo 2 p 677689 2000). This base sequence (12) is published on the book database (www cb gov) with the accession: A44754.
  • B AC B Ce ado oc y e ac va g C e ok e described in the document corresponds to BRA in this specification. Is.
  • the 300 bp 13 of the open frame shows the column A.
  • C2 2 obtained from the official link.
  • Spe Sc F s S a dcD Killadam mixer (Invisibility) was used to synthesize one cDA, and RTPCR (Reve seT a sc ase Po y e aseC a Reac o).
  • the produced D A piece was microinjected into the C57B 6 mouse embryo. From the mousse obtained by transplanting the eggs containing D A into the pseudo-us palace, we selected the ones containing the target D A pieces, and used this as the first generation C BRA Rasius.
  • C2C12 obtained from a concrete tank, was cultivated at 4 D beccos od esEages e (D E) land to induce oxidization.
  • D E D beccos od esEages e
  • the myocytes were treated with 100 Us BRA (R DSys e s) and further supplemented with 0 Is and stimulated at 37C.
  • BRA was not used, and BRA was also added.
  • These cells were thawed and 20 tank compounds were subjected to SDS aqua and subjected to Western analysis with Se 473 and (Ce S ag).
  • PB proteinase B
  • PB proteinase B
  • the number of courages of the grown BRA quaau CB Langsickus is It was 44 less than the number of quadruple Quars raised. Although this does not indicate that the BRA-induced guidance in obesity is a full contributor to the disease, the BRA does indicate that the crew members have a different sex. . This was attached by the results of experiments in which BRA directly impairs the insulin signatures for C2C 2 cells.
  • the knockout object in which the BRA gene was destroyed that is, the lost object of BRA CXC 4 is provided. It is extremely useful for clarification of cerebral BAR of white globules, white globules and quats, and for urinary BAR of 2 urinary diseases that are mainly caused by insulin.
  • Ming a method of skating BR Antas will be provided. Singing of Ming By using a substance of the present invention that can survive for a long period of time and a control substance (in both states), it is possible to easily evaluate that the candidate substance is the BRA substance ant. It is useful. In addition, Ming provides a method for determining the action of BR anatase using Ming lantern control lantern.

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Abstract

La présente invention concerne un animal non humain à inactivation du gène BRAK. Cet animal non humain à inactivation du gène BRAK se caractérise en ce que le gène BRAK y a été neutralisé.
PCT/JP2006/324622 2005-12-06 2006-12-05 Animal non humain a inactivation du gene brak WO2007066794A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008096905A1 (fr) * 2007-02-09 2008-08-14 Tokyo Metropolitan Organization For Medical Research Anticorps monoclonal humain anti-brak (cxcl14) et son utilisation
JP2012012330A (ja) * 2010-06-30 2012-01-19 Kanagawa Dental College 癌転移抑制剤及び医薬組成物
US8981899B2 (en) 2007-07-18 2015-03-17 Iloq Oy Electromechanical lock

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008096905A1 (fr) * 2007-02-09 2008-08-14 Tokyo Metropolitan Organization For Medical Research Anticorps monoclonal humain anti-brak (cxcl14) et son utilisation
US8981899B2 (en) 2007-07-18 2015-03-17 Iloq Oy Electromechanical lock
JP2012012330A (ja) * 2010-06-30 2012-01-19 Kanagawa Dental College 癌転移抑制剤及び医薬組成物

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