CA2221986A1 - Procede d'identification de therapies de la maladie d'alzheimer a l'aide de modeles animaux transgeniques - Google Patents

Procede d'identification de therapies de la maladie d'alzheimer a l'aide de modeles animaux transgeniques Download PDF

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Publication number
CA2221986A1
CA2221986A1 CA002221986A CA2221986A CA2221986A1 CA 2221986 A1 CA2221986 A1 CA 2221986A1 CA 002221986 A CA002221986 A CA 002221986A CA 2221986 A CA2221986 A CA 2221986A CA 2221986 A1 CA2221986 A1 CA 2221986A1
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Canada
Prior art keywords
app
beta
glu
mammal
amino acid
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Abandoned
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CA002221986A
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English (en)
Inventor
Lisa Claire Mcconlogue
Peter A. Seubert
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Athena Neurosciences Inc
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Individual
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Publication of CA2221986A1 publication Critical patent/CA2221986A1/fr
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • 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
    • 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
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • 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
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • 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
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • 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
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • 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
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0306—Animal model for genetic diseases
    • A01K2267/0312—Animal model for Alzheimer's disease
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Neurology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Neurosurgery (AREA)
  • Wood Science & Technology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Hospice & Palliative Care (AREA)
  • General Chemical & Material Sciences (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne la construction de modèles animaux transgéniques pour tester d'éventuels traitements de la maladie d'Alzheimer. Ces modèles se caractérisent par une pathologie similaire à celle observée dans la maladie d'Alzheimer, fondée sur l'expression des trois formes de la protéine précurseur de .beta.-amyloïde (APP), APP695, APP751 et APP770, de même que diverses mutations ponctuelles fondées sur des mutations se produisant naturellement, telles que les mutations au niveau de l'aminoacide 717 de la maladie d'Alzheimer familiale (FAD) de type London et Indiana, les mutations prédites du gène d'APP et les formes tronquées d'APP contenant la région A.beta.. Les produits de recombinaison génique d'APP sont obtenus à l'aide du promoteur génique de la chaîne du facteur B de croissance dérivé de plaquettes humaines (PDGF-B) ou d'autres promoteurs aptes à exprimer l'A.beta. ou des formes mutantes d'APP à un niveau élevé dans le tissu cérébral d'animaux transgéniques. Des cellules animales peuvent être isolées d'animaux transgéniques ou préparés à l'aide des mêmes produits de recombinaison avec des techniques standard, telles que la lipofection ou l'électroporation. Les animaux transgéniques ou les cellules animales sont utilisés pour examiner les composés qui modifient l'évolution pathologique de la maladie d'Alzheimer, qui peut être mesurée par les effets sur la quantité d'APP et de peptide de .beta.-amyloïde, la neuropathologie et les modifications comportementales.
CA002221986A 1995-06-07 1996-06-07 Procede d'identification de therapies de la maladie d'alzheimer a l'aide de modeles animaux transgeniques Abandoned CA2221986A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US48653895A 1995-06-07 1995-06-07
US48601895A 1995-06-07 1995-06-07
US486,538 1995-06-07
US486,018 1995-06-07

Publications (1)

Publication Number Publication Date
CA2221986A1 true CA2221986A1 (fr) 1996-12-19

Family

ID=27048545

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002221986A Abandoned CA2221986A1 (fr) 1995-06-07 1996-06-07 Procede d'identification de therapies de la maladie d'alzheimer a l'aide de modeles animaux transgeniques

Country Status (5)

Country Link
EP (1) EP0832205A1 (fr)
JP (1) JP2001517065A (fr)
AU (1) AU6264996A (fr)
CA (1) CA2221986A1 (fr)
WO (1) WO1996040895A1 (fr)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999009150A1 (fr) * 1996-08-15 1999-02-25 Bayer Corporation Methode permettant d'introduire des modifications dans un gene
US7226730B1 (en) 1997-02-26 2007-06-05 The General Hospital Corporation Transgenic animals and cell lines for screening drugs effective for the treatment or prevention of Alzheimer's Disease
JP4194664B2 (ja) 1997-02-26 2008-12-10 ザ ジェネラル ホスピタル コーポレイション アルツハイマー病の処置または予防のために効果的な薬物をスクリーニングするためのトランスジェニック動物および細胞株
US6175057B1 (en) 1997-10-08 2001-01-16 The Regents Of The University Of California Transgenic mouse model of alzheimer's disease and cerebral amyloid angiopathy
US6455757B1 (en) 1997-10-08 2002-09-24 The Regents Of The University Of California Transgenic mice expressing human APP and TGF-β demonstrate cerebrovascular amyloid deposits
TWI239847B (en) 1997-12-02 2005-09-21 Elan Pharm Inc N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease
US20080050367A1 (en) 1998-04-07 2008-02-28 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
US6046381A (en) * 1998-04-30 2000-04-04 The Regents Of The University Of California Apolipoprotein E transgenic mice and assay methods
WO2000059297A2 (fr) * 1999-04-06 2000-10-12 Harrington Arthritis Research Center Methodes permettant de suivre l'evolution de la maladie d'alzheimer et d'identifier des traitements au moyen de souris transgeniques
SI1292187T1 (sl) * 2000-06-20 2006-10-31 Univ Toronto Transgenski zivalski model nevrodegenerativnih motenj
US7371920B2 (en) 2000-06-20 2008-05-13 The Governing Council Of The University Of Toronto Transgenic mouse model of neurodegenerative disorders
MY139983A (en) 2002-03-12 2009-11-30 Janssen Alzheimer Immunotherap Humanized antibodies that recognize beta amyloid peptide
US7217262B2 (en) 2003-01-17 2007-05-15 The Procter & Gamble Co. Absorbent article having stretchable fastening member
KR100574544B1 (ko) * 2004-04-01 2006-04-27 주식회사 뉴로테크 돌연변이 βＣＴＦ99를 발현하는 알츠하이머병 유발형질전환 마우스
JP2008523815A (ja) 2004-12-15 2008-07-10 エラン ファーマ インターナショナル リミテッド 認知の改善における使用のためのヒト化アミロイドβ抗体
EP1999144A1 (fr) 2006-03-16 2008-12-10 VIB vzw Mutations de promoteur qui augmentent l'expression de la protéine précurseur d'amyloïde
US8784810B2 (en) 2006-04-18 2014-07-22 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
US8003097B2 (en) 2007-04-18 2011-08-23 Janssen Alzheimer Immunotherapy Treatment of cerebral amyloid angiopathy
JO3076B1 (ar) 2007-10-17 2017-03-15 Janssen Alzheimer Immunotherap نظم العلاج المناعي المعتمد على حالة apoe
US9067981B1 (en) 2008-10-30 2015-06-30 Janssen Sciences Ireland Uc Hybrid amyloid-beta antibodies
WO2013041577A1 (fr) 2011-09-20 2013-03-28 Vib Vzw Procédés de diagnostic de la sclérose latérale amyotrophique et de la dégénérescence lobaire frontotemporale

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE286971T1 (de) * 1991-01-21 2005-01-15 Elan Pharm Inc Prüfung und modell für alzheimers-krankheit
WO1993007296A1 (fr) * 1991-10-03 1993-04-15 Indiana University Foundation Procede pour depister la maladie d'alzheimer
CA2127450C (fr) * 1992-01-07 2007-04-17 Samuel Wadsworth Modeles d'animaux transgeniques pour la maladie d'alzheimer
EP0561087B1 (fr) * 1992-03-20 1999-08-04 N.V. Innogenetics S.A. Forme mutée du gène de la protéine du précurseur beta-amyloide
US5604102A (en) * 1992-04-15 1997-02-18 Athena Neurosciences, Inc. Methods of screening for β-amyloid peptide production inhibitors
WO1994023049A2 (fr) * 1993-04-02 1994-10-13 The Johns Hopkins University Introduction et expression de grandes sequences genomiques chez des animaux transgeniques
CA2174429C (fr) * 1993-10-27 2011-08-30 Lisa C. Mcconlogue Animaux transgeniques hebergeant un gene allele app presentant une mutation suedoise
WO1995014769A1 (fr) * 1993-11-29 1995-06-01 University Of South Florida Souris transgenique preparee a l'aide de chromosomes artificiels de levure et d'une recombinaison homologue
DE69533583T2 (de) * 1994-01-27 2005-10-06 Regents of the University of Minnesota, Southeast, Minneapolis Nicht humane, transgenische säugetiere mit sich entwickelnder neurologischer krankheit

Also Published As

Publication number Publication date
JP2001517065A (ja) 2001-10-02
WO1996040895A1 (fr) 1996-12-19
EP0832205A1 (fr) 1998-04-01
AU6264996A (en) 1996-12-30

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