CA2301871A1 - Alteration fonctionnelle du gene brca2 dans des cellules et des animaux transgeniques non humains - Google Patents

Alteration fonctionnelle du gene brca2 dans des cellules et des animaux transgeniques non humains Download PDF

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Publication number
CA2301871A1
CA2301871A1 CA002301871A CA2301871A CA2301871A1 CA 2301871 A1 CA2301871 A1 CA 2301871A1 CA 002301871 A CA002301871 A CA 002301871A CA 2301871 A CA2301871 A CA 2301871A CA 2301871 A1 CA2301871 A1 CA 2301871A1
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Canada
Prior art keywords
brca2
cells
gene
impaired
mutation
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Abandoned
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CA002301871A
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English (en)
Inventor
Paul Hasty
Greg Donoho
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Lexicon Pharmaceuticals Inc
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Individual
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Publication of CA2301871A1 publication Critical patent/CA2301871A1/fr
Abandoned legal-status Critical Current

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    • 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; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027New or modified breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • 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
    • C07K14/4702Regulators; Modulating activity
    • C07K14/4703Inhibitors; Suppressors
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; 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; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/07Animals genetically altered by homologous recombination
    • A01K2217/075Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; 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; AVICULTURE; APICULTURE; PISCICULTURE; 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
    • A01K2267/0331Animal model for proliferative diseases

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Environmental Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Animal Husbandry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

ScRad51, élément du groupe épistatique RAD52 de Saccharomyces cerevisiae, est un composant important de la voie de réparation par recombinaison utilisé pour réparer les dégâts génétiques provoqués par les rayonnements ionisants. L'homologue murin de ScRad51, MmRad51, semble posséder une fonction similaire; cependant le mécanisme précis d'action n'est pas bien compris. Les associations protéine:protéine sont critiques pour la fonction de ScRad51. Par conséquent, on a utilisé le système de levure à deux hybrides pour isoler des protéines qui s'associent à MmRad51, dans le but de mieux comprendre la réparation par recombinaison dans les cellules mammaliennes et l'on a isolé le Brca2 murin. Chez les humains, BRCA2 est un gène suppresseur de tumeur, important dans l'étiologie du cancer du sein. Une comparaison phénotypique entre MmRad51 et des embryons et des cellules présentant une carence en Brca2 suggère que l'association protéine:protéine est importante pour leur fonction. De même que pour MmRad51, la fonction du Brca2 est critique s'agissant de la réparation des dégâts occasionnés par les rayonnements gamma. En outre, une mutation subtile qui retire seulement la petite fraction de Brca2 qui s'associe à MmRad51, soit directement soit indirectement, présente un phénotype qui suggère une fonction partielle. Ces cellules mutantes homozygotes sont viables, quoiqu'hypersensibles aux rayonnements ionisants et subissent une sénescence réplicative prématurée. On a ainsi créé des cellules et des souris présentant une altération fonctionnelle du gène Brca2, qui devraient s'avérer utiles en tant que modèle tumorigène destiné à l'analyse d'agents génotoxiques et en tant qu'outil d'étude de la sénescence réplicative prématurée.
CA002301871A 1997-08-26 1998-08-25 Alteration fonctionnelle du gene brca2 dans des cellules et des animaux transgeniques non humains Abandoned CA2301871A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5697397P 1997-08-26 1997-08-26
US60/056,973 1997-08-26
PCT/US1998/017566 WO1999010479A1 (fr) 1997-08-26 1998-08-25 Alteration fonctionnelle du gene brca2 dans des cellules et des animaux transgeniques non humains

Publications (1)

Publication Number Publication Date
CA2301871A1 true CA2301871A1 (fr) 1999-03-04

Family

ID=22007720

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002301871A Abandoned CA2301871A1 (fr) 1997-08-26 1998-08-25 Alteration fonctionnelle du gene brca2 dans des cellules et des animaux transgeniques non humains

Country Status (5)

Country Link
EP (1) EP1025203A4 (fr)
JP (1) JP2001513991A (fr)
AU (1) AU757433B2 (fr)
CA (1) CA2301871A1 (fr)
WO (1) WO1999010479A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU778719B2 (en) 1999-07-14 2004-12-16 Transgenic Inc. Trap vector and gene trapping method by using the same
US6531644B1 (en) * 2000-01-14 2003-03-11 Exelixis, Inc. Methods for identifying anti-cancer drug targets
JP2001211882A (ja) * 2000-01-31 2001-08-07 Shiyuuji Miyagawa 移植関連タンパク質をコードするコドン改変型遺伝子
CA2432976A1 (fr) * 2000-12-21 2002-08-08 Board Of Trustees Of The University Of Illinois Reactifs et procedes d'identification et de modulation de l'expression de genes de senescence tumorale
AU2002359398A1 (en) * 2001-11-16 2003-06-10 Exelixis, Inc. Nucleic acids and polypeptides of invertebrate brca2 and methods of use

Also Published As

Publication number Publication date
EP1025203A1 (fr) 2000-08-09
JP2001513991A (ja) 2001-09-11
EP1025203A4 (fr) 2003-06-04
WO1999010479A1 (fr) 1999-03-04
AU9033498A (en) 1999-03-16
AU757433B2 (en) 2003-02-20

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EEER Examination request
FZDE Discontinued
FZDE Discontinued

Effective date: 20070827