WO2002008407A3 - Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring - Google Patents

Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring Download PDF

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Publication number
WO2002008407A3
WO2002008407A3 PCT/US2001/022693 US0122693W WO0208407A3 WO 2002008407 A3 WO2002008407 A3 WO 2002008407A3 US 0122693 W US0122693 W US 0122693W WO 0208407 A3 WO0208407 A3 WO 0208407A3
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WO
WIPO (PCT)
Prior art keywords
gene
human
mutation
human mammal
fad
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Application number
PCT/US2001/022693
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French (fr)
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WO2002008407A2 (en
WO2002008407A9 (en
Inventor
Richard W Scott
Andrew G Reaume
Karen Dorfman
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Cephalon Inc
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
Priority claimed from US09/621,897 external-priority patent/US6734336B1/en
Application filed by Cephalon Inc filed Critical Cephalon Inc
Priority to JP2002513891A priority Critical patent/JP5046413B2/en
Priority to AU7699501A priority patent/AU7699501A/en
Priority to CA002416381A priority patent/CA2416381A1/en
Priority to AU2001276995A priority patent/AU2001276995C1/en
Priority to EP01954771A priority patent/EP1304922A2/en
Publication of WO2002008407A2 publication Critical patent/WO2002008407A2/en
Publication of WO2002008407A3 publication Critical patent/WO2002008407A3/en
Publication of WO2002008407A9 publication Critical patent/WO2002008407A9/en

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    • 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
    • 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
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • 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
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • 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
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Medicinal Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Hematology (AREA)
  • Neurosurgery (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Cell Biology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Pathology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Toxicology (AREA)
  • Food Science & Technology (AREA)
  • Animal Husbandry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hospice & Palliative Care (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)

Abstract

The present invention provides a gene-targeted, non-human mammal having a gene encoding a mutant protein product of a mutated FAD presenilin-1 (PS-1) gene, a human FAD Swedish mutation, and a humanized Aβ mutation, and generational offspring thereof and a gene-targeted, non-human mammal having a gene encoding a mutant protein product of a mutated FAD PS-1 gene and a human Swedish APP695 mutation, and generational offspring thereof, as well as methods of identifying compounds useful in treating Alzheimer's disease, and to methods of treating Alzheimer's disease.
PCT/US2001/022693 2000-07-20 2001-07-19 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring WO2002008407A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2002513891A JP5046413B2 (en) 2000-07-20 2001-07-19 Targeted recombinant non-human mammal with human FAD presenilin mutation and reproductive progeny
AU7699501A AU7699501A (en) 2000-07-20 2001-07-19 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring
CA002416381A CA2416381A1 (en) 2000-07-20 2001-07-19 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring
AU2001276995A AU2001276995C1 (en) 2000-07-20 2001-07-19 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring
EP01954771A EP1304922A2 (en) 2000-07-20 2001-07-19 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/621,897 US6734336B1 (en) 1997-08-29 2000-07-20 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring
US09/621,897 2000-07-20

Publications (3)

Publication Number Publication Date
WO2002008407A2 WO2002008407A2 (en) 2002-01-31
WO2002008407A3 true WO2002008407A3 (en) 2003-01-09
WO2002008407A9 WO2002008407A9 (en) 2003-02-27

Family

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Family Applications (1)

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PCT/US2001/022693 WO2002008407A2 (en) 2000-07-20 2001-07-19 Gene-targeted non-human mammal with human fad presenilin mutation and generational offspring

Country Status (5)

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EP (1) EP1304922A2 (en)
JP (1) JP5046413B2 (en)
AU (2) AU2001276995C1 (en)
CA (1) CA2416381A1 (en)
WO (1) WO2002008407A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2856409B1 (en) * 2003-06-20 2007-08-31 Aventis Pharma Sa METHODS OF DETECTING ALZHEIMER'S DISEASE
FR2860391B1 (en) * 2003-10-02 2006-01-27 Aventis Pharma Sa TRANSGENIC ANIMALS WITH MAJOR DISORDERS RELATED TO ALZHEIMER'S DISEASE
WO2007134272A2 (en) * 2006-05-12 2007-11-22 Janssen Pharmaceutica N.V. Humanized models via targeted mtagenesis with zinc finger nuclease

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996034097A1 (en) * 1995-04-26 1996-10-31 Cephalon, Inc. GENE-TARGETED NON-HUMAN MAMMALS DEFICIENT IN SOD-1 GENE AND EXPRESSING HUMANIZED Aβ SEQUENCE WITH SWEDISH FAD MUTATION
US5898094A (en) * 1996-10-21 1999-04-27 University Of South Florida Transgenic mice expressing APPK670N,M671L and a mutant presenilin transgenes
WO1999034670A1 (en) * 1998-01-08 1999-07-15 Daiichi Pharmaceutical Co., Ltd. Gene mutant animals

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US589094A (en) * 1897-08-31 Jacob ormerod

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996034097A1 (en) * 1995-04-26 1996-10-31 Cephalon, Inc. GENE-TARGETED NON-HUMAN MAMMALS DEFICIENT IN SOD-1 GENE AND EXPRESSING HUMANIZED Aβ SEQUENCE WITH SWEDISH FAD MUTATION
US5898094A (en) * 1996-10-21 1999-04-27 University Of South Florida Transgenic mice expressing APPK670N,M671L and a mutant presenilin transgenes
WO1999034670A1 (en) * 1998-01-08 1999-07-15 Daiichi Pharmaceutical Co., Ltd. Gene mutant animals
EP1044605A1 (en) * 1998-01-08 2000-10-18 Daiichi Pharmaceutical Co., Ltd. Gene mutant animals

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BORCHELT D. R. ET AL.: "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursors proteins.", NEURON, vol. 19, no. 4, 1997, pages 939 - 945, XP002204784, ISSN: 0896-6273 *
FLOOD D. G. ET AL.: "FAD mutant PS-1 gene-targeted mice: Increased Abeta42 and Abeta deposition without APP overproduction.", NEUROBIOLOGY OF AGING, vol. 23, no. 3, May 2002 (2002-05-01), pages 335 - 348, XP002204785, ISSN: 0197-4580 *
REAUME A. G. ET AL.: "Enhanced amyloidogenic processing of the beta-amyloid precursor protein in gene-targeted mice bearing the Swedish familial Alzheimer's disease mutations and a "humanized" A-beta sequence.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 271, no. 38, 1996, pages 23380 - 23388, XP002204783, ISSN: 0021-9258 *
SIMAN R. ET AL.: "Presenilin-1 P264L knock-in mutation: Effect on cortical neuronal vulnerability to degeneration.", SOCIETY FOR NEUROSCIENCE ABSTRACTS., vol. 25, no. 1-2, 23 October 1999 (1999-10-23), pages 1046, XP001089602, ISSN: 0190-5295 *

Also Published As

Publication number Publication date
WO2002008407A2 (en) 2002-01-31
CA2416381A1 (en) 2002-01-31
JP2004533802A (en) 2004-11-11
AU2001276995B2 (en) 2006-02-02
JP5046413B2 (en) 2012-10-10
WO2002008407A9 (en) 2003-02-27
AU7699501A (en) 2002-02-05
AU2001276995C1 (en) 2006-10-26
EP1304922A2 (en) 2003-05-02

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