WO1994023049A3 - The introduction and expression of large genomic sequences in transgenic animals - Google Patents

The introduction and expression of large genomic sequences in transgenic animals Download PDF

Info

Publication number
WO1994023049A3
WO1994023049A3 PCT/US1994/003619 US9403619W WO9423049A3 WO 1994023049 A3 WO1994023049 A3 WO 1994023049A3 US 9403619 W US9403619 W US 9403619W WO 9423049 A3 WO9423049 A3 WO 9423049A3
Authority
WO
WIPO (PCT)
Prior art keywords
app
gene
yac
expression
transgenic mice
Prior art date
Application number
PCT/US1994/003619
Other languages
French (fr)
Other versions
WO1994023049A2 (en
WO1994023049A9 (en
Inventor
John D Gearhart
Bruce T Lamb
Original Assignee
Univ Johns Hopkins
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Johns Hopkins filed Critical Univ Johns Hopkins
Publication of WO1994023049A2 publication Critical patent/WO1994023049A2/en
Publication of WO1994023049A9 publication Critical patent/WO1994023049A9/en
Publication of WO1994023049A3 publication Critical patent/WO1994023049A3/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027New breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278Humanized animals, e.g. knockin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711Alzheimer's disease; Amyloid plaque core protein
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00Modified animals
    • A01K2207/15Humanized animals
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/05Animals comprising random inserted nucleic acids (transgenic)
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/0306Animal model for genetic diseases
    • A01K2267/0312Animal model for Alzheimer's disease
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/035Animal model for multifactorial diseases
    • A01K2267/0381Animal model for diseases of the hematopoietic system

Abstract

This invention provides a method for the efficient introduction of cloned, very high molecular weight DNA into the germline of mice, whereby large genes can be expressed appropriately in transgenic mice. The β-amyloid precursor protein (APP) is known to be a complex gene consisting of 18 exons with total size estimates greater than 170 kb encoding three major RNA splicing forms. According to this invention, a neomycin resistance cassette is introduced into one of the arms of a 650 kb yeast artificial chromosome (YAC) which contains the entire unrearranged APP gene within 400 kb. Following gel purification, the YAC is introduced into embryonic stem (ES) cells by lipid mediated transfection. Neomycin resistant ES lines are isolated with the human APP gene stably integrated in an unrearranged state and expressing properly initiated and spliced full length human APP mRNA and APP human protein. Mouse chimeras generated from these ES lines transmit the YAC to their offspring, generating novel APP YAC transgenic mice. These transgenic mice express human APP gene products at significant levels in brain and peripheral tissues that mirror the expression of endogenous mouse APP gene products. This procedure will have great utility for transgenic studies of gene expression involving large genes and gene complexes.
PCT/US1994/003619 1993-04-02 1994-04-01 The introduction and expression of large genomic sequences in transgenic animals WO1994023049A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4239093A 1993-04-02 1993-04-02
US08/042,390 1993-04-02

Publications (3)

Publication Number Publication Date
WO1994023049A2 WO1994023049A2 (en) 1994-10-13
WO1994023049A9 WO1994023049A9 (en) 1994-11-24
WO1994023049A3 true WO1994023049A3 (en) 1995-01-05

Family

ID=21921669

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/003619 WO1994023049A2 (en) 1993-04-02 1994-04-01 The introduction and expression of large genomic sequences in transgenic animals

Country Status (1)

Country Link
WO (1) WO1994023049A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8877175B2 (en) 2006-09-14 2014-11-04 Medgenics Medical Israel Ltd. Long lasting drug formulations
US9127084B2 (en) 2006-09-14 2015-09-08 Medgenics Medical Israel Ltd. Long lasting drug formulations

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9119338D0 (en) * 1991-09-10 1991-10-23 Inst Of Animal Physiology And Control of gene expression
JPH07506720A (en) * 1992-01-07 1995-07-27 アテナ ニューロサイエンシーズ, インコーポレイテッド Transgenic animal model of Alzheimer's disease
US6610493B1 (en) 1993-06-17 2003-08-26 Brigham And Women's Hospital Screening compounds for the ability to alter the production of amyloid-β peptide
US6264915B1 (en) 1992-09-13 2001-07-24 The President And Fellows Of Harvard College Process for detecting potential carcinogens
JPH09507746A (en) * 1993-10-27 1997-08-12 アテナ ニューロサイエンシズ,インコーポレイティド Transgenic animal containing APP allele with Swedish mutation
US6025183A (en) * 1994-02-28 2000-02-15 Yissum Research Development Company Of The Hebrew University Of Jerusalem Transgenic animal assay system for anti-cholinesterase substances
WO1995034640A1 (en) * 1994-06-13 1995-12-21 Henry Ford Health System A novel neuronal-neonatal gene: neuronatin
US6531586B1 (en) 1995-04-28 2003-03-11 The Hospital For Sick Children Genetic sequences related to Alzheimer's Disease
US5986054A (en) 1995-04-28 1999-11-16 The Hospital For Sick Children, Hsc Research And Development Limited Partnership Genetic sequences and proteins related to alzheimer's disease
US6210919B1 (en) 1995-04-28 2001-04-03 Hsc Research And Development Limited Partnership Genetic sequences and proteins related to alzheimer's disease
US5777093A (en) * 1995-05-16 1998-07-07 Ramot-University Authority For Applied Research & Industrial Development Ltd. cDNAs associated with ataxia-telangiectasia
US5858661A (en) * 1995-05-16 1999-01-12 Ramot-University Authority For Applied Research And Industrial Development Ataxia-telangiectasia gene and its genomic organization
US5728807A (en) * 1995-05-16 1998-03-17 Ramot-University Authority For Applied Research And Industrial Development, Ltd. Mutated proteins associated with ataxia-telangiectasia
JPH11507821A (en) * 1995-06-07 1999-07-13 アセナ ニューロサイエンシーズ,インコーポレイテッド Methods for identifying therapeutic agents for Alzheimer's disease using transgenic animal models
CA2221986A1 (en) * 1995-06-07 1996-12-19 Athena Neurosciences, Inc. Method for identifying alzheimer's disease therapeutics using transgenic animal models
US6717031B2 (en) 1995-06-07 2004-04-06 Kate Dora Games Method for selecting a transgenic mouse model of alzheimer's disease
WO1997027296A1 (en) * 1996-01-26 1997-07-31 Hsc Research And Development Limited Partnership Nucleic acids and proteins related to alzheimer's disease, and uses therefor
US6140309A (en) * 1996-03-12 2000-10-31 University Of South Florida Vasoactive effects and free radical generation by β-amyloid peptides
US6077697A (en) * 1996-04-10 2000-06-20 Chromos Molecular Systems, Inc. Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
US6025155A (en) * 1996-04-10 2000-02-15 Chromos Molecular Systems, Inc. Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
JP2000513230A (en) 1996-07-01 2000-10-10 エイ. ライト,ジム Oligonucleotides from the untranslated region of a housekeeping gene and methods of using the same to regulate cell growth
WO1999009150A1 (en) * 1996-08-15 1999-02-25 Bayer Corporation Method of introducing modifications into a gene
US5898094A (en) * 1996-10-21 1999-04-27 University Of South Florida Transgenic mice expressing APPK670N,M671L and a mutant presenilin transgenes
EP1707051B1 (en) * 1997-02-28 2010-01-13 Kyowa Hakko Kirin Co., Ltd. Human chromosome fragment, and vector containing it
US7973156B2 (en) 1997-08-21 2011-07-05 Quark Pharmaceuticals Inc. Hypoxia-regulated genes
JP4354633B2 (en) 1997-08-21 2009-10-28 クアーク ファーマシューティカルズ、インコーポレイテッド Hypoxia-regulated gene
CA2318479C (en) 1998-01-12 2009-03-24 Georgetown University Medical Center G protein-related kinase mutants in essential hypertension
US6787318B1 (en) 1999-06-01 2004-09-07 Roskamp Research Institute, Llc Assay for evaluating the therapeutic effectiveness of agents in reducing Alzheimer's disease pathology
US6875582B1 (en) 1999-08-19 2005-04-05 Omniscience Pharmaceuticals, Inc. Methods and targets of antibiotic resistance
EP1252292A4 (en) 2000-01-24 2004-11-17 Univ Ramot Plants tolerant of environmental stress conditions, methods of generating same and novel polynucleotide sequence utilized thereby
HUP0300810A2 (en) 2000-07-20 2003-08-28 M.G.V.S. Ltd. Artifical vascular grafts, and methods of producing and using same
US20040037828A1 (en) 2002-07-09 2004-02-26 Bar-Ilan University Methods and pharmaceutical compositions for healing wounds
EP2138583A1 (en) 2000-12-22 2009-12-30 Institut National De La Recherche Agronomique Position-independent and tissue specific expression of a transgene in milk of transgenic animals
CA2441937A1 (en) * 2001-05-30 2002-12-05 Chromos Molecular Systems, Inc. Chromosome-based platforms
US8178128B2 (en) 2001-12-05 2012-05-15 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Nanoparticles containing polymeric nucleic acid homologs
US6992176B2 (en) 2002-02-13 2006-01-31 Technion Research & Development Foundation Ltd. Antibody having a T-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease
ES2245591B1 (en) 2004-04-06 2007-04-01 Consejo Sup. Investigaciones Cientificas NEW PROCEDURE FOR GENERATING NON-HUMAN TRANSGENIC ANIMALS, AND THE TRANSGENIC ANIMALS SO OBTAINED.
ES2679282T3 (en) 2004-10-22 2018-08-23 Revivicor Inc. Transgenic pigs that lack endogenous immunoglobulin light chain
ES2316209B1 (en) * 2005-12-02 2009-11-13 Universidad Autonoma De Madrid ANZAL MODEL OF ALZHEIMER'S DISEASE, PROCEDURE OF OBTAINING AND ITS APPLICATIONS.
WO2007088418A1 (en) 2006-01-31 2007-08-09 Multi Gene Vascular Systems, Inc. Drug-eluting intravascular prostheses and methods of use
AU2007294858B2 (en) 2006-09-14 2011-05-12 Medgenics Medical Israel, Ltd Long lasting drug formulations
WO2008068024A2 (en) * 2006-12-06 2008-06-12 Universität Zürich Means and methods for isolating and determining novel targets for the treatment of neurodegenerative, neurological or neuropsychiatric disorders and compositions comprising the same
WO2008152507A2 (en) 2007-03-16 2008-12-18 Multigene Vascular Systems, Inc. Compositions and methods for treating ophthalmic disorders
CA2682093A1 (en) 2007-03-29 2008-10-09 Technion Research & Development Foundation Ltd. Antibodies, methods and kits for diagnosing and treating melanoma
DK2348827T3 (en) 2008-10-27 2015-07-20 Revivicor Inc IMMUNICIPLY COMPROMATED PETS
EP3060144A1 (en) 2013-10-24 2016-08-31 Medgenics Medical Israel, Ltd Micro-organs providing sustained delivery of a therapeutic polypeptide and methods of use thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0518583A1 (en) * 1991-06-13 1992-12-16 Zeneca Limited Nucleotide sequences
WO1993005165A1 (en) * 1991-09-10 1993-03-18 Agriculture And Food Research Council Yeast artificial chromosomes and their use in the control of gene expression
WO1994000569A1 (en) * 1992-06-18 1994-01-06 Genpharm International, Inc. Methods for producing transgenic non-human animals harboring a yeast artificial chromosome

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0518583A1 (en) * 1991-06-13 1992-12-16 Zeneca Limited Nucleotide sequences
WO1993005165A1 (en) * 1991-09-10 1993-03-18 Agriculture And Food Research Council Yeast artificial chromosomes and their use in the control of gene expression
WO1994000569A1 (en) * 1992-06-18 1994-01-06 Genpharm International, Inc. Methods for producing transgenic non-human animals harboring a yeast artificial chromosome

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
B.E. PEARSON AND T.K. CHOI: "Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice", PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 10578 - 10582 *
B.T. LAMB AND J.H. GEARHART: "Characterization and manipulation of yeast artificial chromosomes containing the human amyloid precursor protein gene", J. CELL. BIOCHEM. SUPPL. 0 (16 PART E), 1992, pages 212 *
B.T. LAMB ET AL.;: "Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice", NATURE GENETICS, vol. 5, 1993, pages 22 - 30 *
Keystone Symposium on advances in under- standing neurodegenerative disorders, Big Sky, Montana, USA, March 28 - April 4, 1992. *
W.M. STRAUSS ET AL.;: "Germ line transmission of a yeast artificial chromosome spanning the murine alpha-1(I) collagen locus", SCIENCE, vol. 259, 1993, pages 1904 - 1907 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8877175B2 (en) 2006-09-14 2014-11-04 Medgenics Medical Israel Ltd. Long lasting drug formulations
US9127084B2 (en) 2006-09-14 2015-09-08 Medgenics Medical Israel Ltd. Long lasting drug formulations

Also Published As

Publication number Publication date
WO1994023049A2 (en) 1994-10-13

Similar Documents

Publication Publication Date Title
WO1994023049A3 (en) The introduction and expression of large genomic sequences in transgenic animals
EP1826215B1 (en) Method of obtaining the expression or improving the rate of expression of a gene
Langston et al. Retinoic acid-responsive enhancers located 3 of the Hox A and Hox B homeobox gene clusters: functional analysis
Kollias et al. Regulated expression of human Aγ-, β-, and hybrid γβ-globin genes in transgenic mice: manipulation of the developmental expression patterns
Harel et al. Efficient genome engineering approaches for the short-lived African turquoise killifish
Klüppel et al. The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina.
Krimpenfort et al. Transcription of T cell receptor beta‐chain genes is controlled by a downstream regulatory element.
Ainscough et al. Imprinting of Igf2 and H19 from a 130 kb YAC transgene
Ariel et al. Methylation patterns of testis-specific genes.
Drewell et al. Deletion of a silencer element disrupts H19 imprinting independently of a DNA methylation epigenetic switch
Kollias et al. Regulated expression of human A?-,?-, and hybrid??-globin genes in transgenic mice: Manipulation of the developmental expression patterns
CN112334157A (en) Compositions and methods for treating spinal muscular atrophy
Brorson et al. Analysis of a new class I gene mapping to the Hmt region of the mouse
Koga et al. Germline transgenesis of zebrafish using the medaka Tol1 transposon system
Dinkel et al. Efficient generation of transgenic BALB/c mice using BALB/c embryonic stem cells
Matsuura et al. Xist expression from an Xist YAC transgene carried on the mouse Y chromosome
Tripathi et al. Definition of a T-cell receptor β gene core enhancer of V (D) J recombination by transgenic mapping
Gerlinger et al. B-lymphocyte targeting of gene expression in transgenic mice with the immunoglobulin heavychain enhancer
KR20100102235A (en) A method to reduce directional bias in transcription
HUP0101961A2 (en) Modifying the expression of the fsh beta gene by homologous recombination
CA2451608C (en) Process for constructing a mutant utilizing the igh 3' enhancer
CN113088537B (en) Construction method and application of TLR9 gene humanized animal model
Cemal et al. Insertion of expanded CAG trinucleotide repeat motifs into a yeast artificial chromosome containing the human Machado–Joseph disease gene
Chong et al. A Functional chromatin domain does not resist X chromosome inactivation: silencing of cLys correlates with methylation of a dual promoter-replication origin
Liebscher et al. Cloning of carp preproinsulin cDNA in the bacterial plasmid pBR322

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

COP Corrected version of pamphlet

Free format text: PAGES 1/14-14/14,DRAWINGS,REPLACED BY NEW PAGES 1/21-21/21;DUE TO LATE TRANSMITTAL BY THE RECEIVINGOFFICE

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA