WO1995020666A3 - Transgenic non-human mammals with progressive neurologic disease - Google Patents

Transgenic non-human mammals with progressive neurologic disease Download PDF

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Publication number
WO1995020666A3
WO1995020666A3 PCT/US1995/001088 US9501088W WO9520666A3 WO 1995020666 A3 WO1995020666 A3 WO 1995020666A3 US 9501088 W US9501088 W US 9501088W WO 9520666 A3 WO9520666 A3 WO 9520666A3
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WO
WIPO (PCT)
Prior art keywords
app
transgenic
disorder
animal
amyloid
Prior art date
Application number
PCT/US1995/001088
Other languages
French (fr)
Other versions
WO1995020666A2 (en
Inventor
Karen Hsiao
David R Borchelt
Sangra M Sisodia
Original Assignee
Univ Minnesota
Karen Hsiao
David R Borchelt
Sangra M Sisodia
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 Minnesota, Karen Hsiao, David R Borchelt, Sangra M Sisodia filed Critical Univ Minnesota
Priority to DE69533583T priority Critical patent/DE69533583T2/en
Priority to AU19096/95A priority patent/AU1909695A/en
Priority to CA002182311A priority patent/CA2182311A1/en
Priority to JP7520186A priority patent/JPH09511388A/en
Priority to EP95911583A priority patent/EP0742831B1/en
Priority to AT95911583T priority patent/ATE278023T1/en
Publication of WO1995020666A2 publication Critical patent/WO1995020666A2/en
Publication of WO1995020666A3 publication Critical patent/WO1995020666A3/en

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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
    • A01K67/0278Knock-in vertebrates, e.g. humanised vertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/0004Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • 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
    • 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
    • A01K2207/00Modified animals
    • A01K2207/15Humanized animals
    • 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
    • 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
    • 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
    • A01K2267/0306Animal model for genetic diseases
    • A01K2267/0312Animal model for Alzheimer's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • 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
    • C12N2830/00Vector systems having a special element relevant for transcription
    • C12N2830/008Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination

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

Abstract

Provided is a transgenic non-human eukaryotic animal whose germ cells and somatic cells contain the amyloid precursor protein sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage. In mice, an age-related CNS disorder characterized by agitation, neophobia, seizures, inactivity, diminished cerebral glucose utilization, cortico-limbic gliosis, and death, develops. An acceleration of this disorder occurs in transgenic mice expressing human and mouse Alzheimer amyloid precursor proteins (APP) produced using a hamster prion protein gene-derived cosmid vector that confers position-independent, copy number-dependent expression. In transgenic mice the disorder develops in direct relationship to brain levels of transgenic APP, but mutant APP confers the phenotype at lower levels of expression than wild-type APP. The disorder occurs in the absence of extracellular amyloid deposition, indicating that some pathogenic activities of APP are dissociated from amyloid formation.
PCT/US1995/001088 1994-01-27 1995-01-27 Transgenic non-human mammals with progressive neurologic disease WO1995020666A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
DE69533583T DE69533583T2 (en) 1994-01-27 1995-01-27 NOT HUMAN, TRANSGENIC MAMMALS WITH DEVELOPING NEUROLOGICAL DISEASE
AU19096/95A AU1909695A (en) 1994-01-27 1995-01-27 Transgenic non-human mammals with progressive neurologic disease
CA002182311A CA2182311A1 (en) 1994-01-27 1995-01-27 Transgenic non-human mammals with progressive neurologic disease
JP7520186A JPH09511388A (en) 1994-01-27 1995-01-27 Nonhuman transgenic mammals with progressive neurological disease
EP95911583A EP0742831B1 (en) 1994-01-27 1995-01-27 Transgenic non-human mammals with progressive neurologic disease
AT95911583T ATE278023T1 (en) 1994-01-27 1995-01-27 NON-HUMAN, TRANSGENIC MAMMALS WITH DEVELOPING NEUROLOGICAL DISEASE

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US18906494A 1994-01-27 1994-01-27
US08/189,064 1994-01-27

Publications (2)

Publication Number Publication Date
WO1995020666A2 WO1995020666A2 (en) 1995-08-03
WO1995020666A3 true WO1995020666A3 (en) 1995-09-28

Family

ID=22695766

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/001088 WO1995020666A2 (en) 1994-01-27 1995-01-27 Transgenic non-human mammals with progressive neurologic disease

Country Status (8)

Country Link
US (1) US6262335B1 (en)
EP (1) EP0742831B1 (en)
JP (1) JPH09511388A (en)
AT (1) ATE278023T1 (en)
AU (1) AU1909695A (en)
CA (1) CA2182311A1 (en)
DE (1) DE69533583T2 (en)
WO (1) WO1995020666A2 (en)

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US5877399A (en) * 1994-01-27 1999-03-02 Johns Hopkins University Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease
US5789655A (en) * 1994-05-13 1998-08-04 The Regents Of The University Of California Transgenic animals expressing artificial epitope-tagged proteins
US5777194A (en) * 1995-04-26 1998-07-07 Cephalon, Inc. Gene-targeted mice with humanized Aβ sequence and Swedish FAD mutation
US6717031B2 (en) 1995-06-07 2004-04-06 Kate Dora Games Method for selecting a transgenic mouse model of alzheimer's disease
CA2221986A1 (en) * 1995-06-07 1996-12-19 Athena Neurosciences, Inc. Method for identifying alzheimer's disease therapeutics using transgenic animal models
WO1999009150A1 (en) * 1996-08-15 1999-02-25 Bayer Corporation Method of introducing modifications into a gene
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US6750324B1 (en) 1997-12-02 2004-06-15 Neuralab Limited Humanized and chimeric N-terminal amyloid beta-antibodies
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US20080050367A1 (en) 1998-04-07 2008-02-28 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
US6787523B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6743427B1 (en) 1997-12-02 2004-06-01 Neuralab Limited Prevention and treatment of amyloidogenic disease
US7964192B1 (en) 1997-12-02 2011-06-21 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidgenic disease
US7790856B2 (en) 1998-04-07 2010-09-07 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
US7179892B2 (en) * 2000-12-06 2007-02-20 Neuralab Limited Humanized antibodies that recognize beta amyloid peptide
US6913745B1 (en) 1997-12-02 2005-07-05 Neuralab Limited Passive immunization of Alzheimer's disease
US6923964B1 (en) 1997-12-02 2005-08-02 Neuralab Limited Active immunization of AScr for prion disorders
US6761888B1 (en) * 2000-05-26 2004-07-13 Neuralab Limited Passive immunization treatment of Alzheimer's disease
US6710226B1 (en) 1997-12-02 2004-03-23 Neuralab Limited Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics
US20030147882A1 (en) * 1998-05-21 2003-08-07 Alan Solomon Methods for amyloid removal using anti-amyloid antibodies
US6787637B1 (en) 1999-05-28 2004-09-07 Neuralab Limited N-Terminal amyloid-β antibodies
UA81216C2 (en) * 1999-06-01 2007-12-25 Prevention and treatment of amyloid disease
EP1248518A2 (en) * 2000-01-21 2002-10-16 PHARMACIA & UPJOHN COMPANY Transgenic mouse model of human neurodegenerative disease
US7371920B2 (en) * 2000-06-20 2008-05-13 The Governing Council Of The University Of Toronto Transgenic mouse model of neurodegenerative disorders
EP1728423B1 (en) * 2000-06-20 2011-03-02 The Governing Council Of The University Of Toronto Transgenic animal model of neurodegenerative disorders
US7700751B2 (en) 2000-12-06 2010-04-20 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize β-amyloid peptide
TWI255272B (en) * 2000-12-06 2006-05-21 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
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US7479579B2 (en) * 2001-12-20 2009-01-20 The Regents Of The University Of California Triple transgenic mouse model of Alzheimer's disease
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WO2003097674A1 (en) * 2002-05-17 2003-11-27 Pipeline Biotech A/S A purified polypeptide, isolated nucleic acids encoding said polypeptide, vectors and use thereof
BRPI0407058A (en) * 2003-02-01 2006-01-17 Neuralab Ltd Methods of prophylaxis and treatment of a disease, pharmaceutical composition, and use of a fragment
TWI374893B (en) 2003-05-30 2012-10-21 Janssen Alzheimer Immunotherap Humanized antibodies that recognize beta amyloid peptide
WO2006066089A1 (en) 2004-12-15 2006-06-22 Neuralab Limited Humanized amyloid beta antibodies for use in improving cognition
TW200636066A (en) * 2004-12-15 2006-10-16 Elan Pharm Inc Humanized antibodies that recognize beta amyloid peptide
US8784810B2 (en) 2006-04-18 2014-07-22 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
JP4942081B2 (en) * 2006-06-20 2012-05-30 独立行政法人理化学研究所 Alzheimer's disease model animals and uses thereof
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JP5889529B2 (en) 2007-07-27 2016-03-22 ヤンセン・サイエンシズ・アイルランド・ユーシー Treatment of amyloidogenic diseases
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Also Published As

Publication number Publication date
DE69533583T2 (en) 2005-10-06
US6262335B1 (en) 2001-07-17
CA2182311A1 (en) 1995-08-03
JPH09511388A (en) 1997-11-18
ATE278023T1 (en) 2004-10-15
EP0742831B1 (en) 2004-09-29
DE69533583D1 (en) 2004-11-04
WO1995020666A2 (en) 1995-08-03
AU1909695A (en) 1995-08-15
EP0742831A1 (en) 1996-11-20

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