WO2001002552A3 - Animaux transgeniques utilises comme modeles dans les maladies neurodegeneratives - Google Patents

Animaux transgeniques utilises comme modeles dans les maladies neurodegeneratives Download PDF

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Publication number
WO2001002552A3
WO2001002552A3 PCT/EP2000/006171 EP0006171W WO0102552A3 WO 2001002552 A3 WO2001002552 A3 WO 2001002552A3 EP 0006171 W EP0006171 W EP 0006171W WO 0102552 A3 WO0102552 A3 WO 0102552A3
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WO
WIPO (PCT)
Prior art keywords
animal
human
protein
sequence
transgenic animals
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PCT/EP2000/006171
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English (en)
Other versions
WO2001002552A2 (fr
Inventor
Hugo Alfons Gabriel Geerts
Koenraad Frederic Fl Spittaels
Den Haute Chris Van
Leuven Freddy Kamiel Van
Original Assignee
Janssen Pharmaceutica Nv
Hugo Alfons Gabriel Geerts
Koenraad Frederic Fl Spittaels
Den Haute Chris Van
Leuven Freddy Kamiel Van
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 GBGB9915574.9A external-priority patent/GB9915574D0/en
Application filed by Janssen Pharmaceutica Nv, Hugo Alfons Gabriel Geerts, Koenraad Frederic Fl Spittaels, Den Haute Chris Van, Leuven Freddy Kamiel Van filed Critical Janssen Pharmaceutica Nv
Priority to JP2001508325A priority Critical patent/JP2003504015A/ja
Priority to AU62673/00A priority patent/AU782281B2/en
Priority to IL14740600A priority patent/IL147406A0/xx
Priority to CA002372742A priority patent/CA2372742A1/fr
Priority to EP00949241A priority patent/EP1216297A2/fr
Priority to NZ515956A priority patent/NZ515956A/en
Publication of WO2001002552A2 publication Critical patent/WO2001002552A2/fr
Publication of WO2001002552A3 publication Critical patent/WO2001002552A3/fr
Priority to NO20020010A priority patent/NO20020010D0/no
Priority to US11/243,412 priority patent/US20060168673A1/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; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276—Knockout animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Humanized animals, e.g. knockin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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
    • A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
    • 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

Abstract

La présente invention concerne un acide nucléique vecteur comprenant : (a) une séquence nucléotidique codant une protéine Tau humaine ; (b) une séquence capable de diriger l'expression de la protéine Tau humaine dans le système nerveux d'un animal non humain ; et (c) une séquence de ciblage qui facilite l'intégration dudit vecteur dans le génome de l'animal afin d'empêcher l'expression de la protéine Tau équivalente ou d'une protéine liée ou équivalente de l'animal en faveur de la protéine Tau humaine. Dans un autre aspect, l'invention concerne un acide nucléique vecteur comprenant : (a) une séquence nucléotidique codant une protéine humaine capable de moduler la protéine Tau humaine ; (b) une séquence capable de diriger l'expression de la protéine précitée dans le système nerveux de l'animal ; et (c) une séquence de ciblage capable de faciliter l'intégration dudit vecteur dans le génome de l'animal facultativement en une position correspondant à une séquence dans l'animal codant un équivalent de la protéine humaine précitée, de façon à empêcher l'expression de la séquence équivalente en faveur de la protéine humaine capable de moduler la protéine Tau humaine. On utilise les vecteurs de l'invention pour fabriquer un animal transgénique non humain en (a) introduisant dans une cellule embryonnaire de l'animal un ou plusieurs acides nucléiques vecteurs décrits ci-dessus ; (b) en introduisant l'embryon de l'étape (a) précitée dans un animal femelle ; (c) en maintenant la femelle dans l'étape (b) jusqu'à ce que l'embryon se soit suffisamment développé et naisse ; et (d) en maintenant en vie l'animal transgénique obtenu.
PCT/EP2000/006171 1999-07-02 2000-06-30 Animaux transgeniques utilises comme modeles dans les maladies neurodegeneratives WO2001002552A2 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2001508325A JP2003504015A (ja) 1999-07-02 2000-06-30 神経変性疾患のモデルとしてのトランスジェニック動物
AU62673/00A AU782281B2 (en) 1999-07-02 2000-06-30 Transgenic animals as models for neurodegenerative disease
IL14740600A IL147406A0 (en) 1999-07-02 2000-06-30 Transgenic animals as models for neurodegenerative disease
CA002372742A CA2372742A1 (fr) 1999-07-02 2000-06-30 Animaux transgeniques doubles utilises comme modeles dans les maladies neurodegenaratives
EP00949241A EP1216297A2 (fr) 1999-07-02 2000-06-30 Animaux transgeniques utilises comme modeles dans les maladies neurodegeneratives
NZ515956A NZ515956A (en) 1999-07-02 2000-06-30 Transgenic animals as models for neurodegenerative disease
NO20020010A NO20020010D0 (no) 1999-07-02 2002-01-02 Transgene dyr som modeller for neurodegenerativ sykdom
US11/243,412 US20060168673A1 (en) 1999-07-02 2005-10-04 Transgenic animals as models for neurodegenerative disease

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9915574.9A GB9915574D0 (en) 1999-07-02 1999-07-02 Transgenic animals as models for neurodegenerative disease
GB9915574.9 1999-07-02
GBGB0002674.0A GB0002674D0 (en) 1999-07-02 2000-02-04 Transgenic animals as models for neurodegenerative disease
GB0002674.0 2000-02-04

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/243,412 Continuation US20060168673A1 (en) 1999-07-02 2005-10-04 Transgenic animals as models for neurodegenerative disease

Publications (2)

Publication Number Publication Date
WO2001002552A2 WO2001002552A2 (fr) 2001-01-11
WO2001002552A3 true WO2001002552A3 (fr) 2001-12-20

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/006171 WO2001002552A2 (fr) 1999-07-02 2000-06-30 Animaux transgeniques utilises comme modeles dans les maladies neurodegeneratives

Country Status (8)

Country Link
EP (1) EP1216297A2 (fr)
JP (1) JP2003504015A (fr)
AU (1) AU782281B2 (fr)
CA (1) CA2372742A1 (fr)
IL (1) IL147406A0 (fr)
NO (1) NO20020010D0 (fr)
NZ (1) NZ515956A (fr)
WO (1) WO2001002552A2 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7799535B1 (en) 1997-12-09 2010-09-21 Arch Development Corporation Methods for identifying factors that control the folding of amyloid proteins of diverse origin
GB0012056D0 (en) * 2000-05-18 2000-07-12 Consejo Superior Investigacion Model for neurodegenerative disease
US7098374B2 (en) * 2001-02-09 2006-08-29 University Of Florida Research Foundation, Inc. Human disease modeling using somatic gene transfer
EP2319936A3 (fr) 2001-02-15 2012-10-17 The University of Chicago Cribles à base de levure pour agents affectant le plissement des protéines
GB0104685D0 (en) * 2001-02-26 2001-04-11 Leuven K U Res & Dev Tau-opathy model
GB0126988D0 (en) * 2001-11-09 2002-01-02 Univ London Disease model
US8288608B2 (en) * 2002-07-12 2012-10-16 Axon Neuroscience Se Transgenic animal expressing alzheimer's tau protein
JP5558049B2 (ja) * 2009-08-21 2014-07-23 泰造 谷口 非ヒトモデル動物を用いたパーキンソン症候群の検査方法
KR101890978B1 (ko) 2014-06-17 2018-08-24 서울대학교산학협력단 알츠하이머 질환 모델용 형질전환 돼지 및 이의 용도

Citations (1)

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Patent Citations (1)

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WO1995005466A1 (fr) * 1993-08-12 1995-02-23 Institute Of Psychiatry Modeles de la maladie d'alzheimer

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Title
29th Annual Meeting of the Society for Neuroscience, Miami Beach, Florida, USA October 23-28 1999 *
BRION J-P ET AL: "TRANSGENIC EXPRESSION OF THE SHORTEST HUMAN TAU AFFECTS ITS COMPARTMENTALIZATION AND ITS PHOSPHORYLATION AS IN THE PRETANGLE STAGE OF ALZHEIMER'S DISEASE", AMERICAN JOURNAL OF PATHOLOGY, PHILADELPHIA, PA, US, vol. 154, no. 1, January 1999 (1999-01-01), pages 255 - 270, XP000965124, ISSN: 0002-9440 *
BROWNLEES J ET AL: "TAU PHOSPHORYLATION IN TRANSGENIC MICE EXPRESSING GLYCOGEN SYNTHASE KINASE-3BETA TRANSGENES", NEUROREPORT,RAPID COMMUNICATIONS OF OXFORD, OXFORD,GB, vol. 8, no. 15, 20 October 1997 (1997-10-20), pages 3251 - 3255, XP000974561, ISSN: 0959-4965 *
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DAWSON, H.N. ETAL.: "Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice", JOURNAL OF CELLULAR BIOLOGY, vol. 114, no. pt 6, March 2001 (2001-03-01), pages 1179 - 1187, XP001020383 *
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Also Published As

Publication number Publication date
IL147406A0 (en) 2002-08-14
NO20020010L (no) 2002-01-02
NO20020010D0 (no) 2002-01-02
JP2003504015A (ja) 2003-02-04
CA2372742A1 (fr) 2001-01-11
WO2001002552A2 (fr) 2001-01-11
EP1216297A2 (fr) 2002-06-26
AU782281B2 (en) 2005-07-14
AU6267300A (en) 2001-01-22
NZ515956A (en) 2004-04-30

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