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WO1999031969A3 - Transgenic animal model for degenerative diseases of cartilage - Google Patents

Transgenic animal model for degenerative diseases of cartilage Download PDF

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Publication number
WO1999031969A3
WO1999031969A3 PCT/US1998/027056 US9827056W WO9931969A3 WO 1999031969 A3 WO1999031969 A3 WO 1999031969A3 US 9827056 W US9827056 W US 9827056W WO 9931969 A3 WO9931969 A3 WO 9931969A3
Authority
WO
WIPO (PCT)
Prior art keywords
cartilage
degenerative disease
animal model
provides
prommp
Prior art date
Application number
PCT/US1998/027056
Other languages
French (fr)
Other versions
WO1999031969A2 (en
Inventor
Lisa Ann Neuhold
Loran Marie Killar
Original Assignee
American Home Prod
Lisa Ann Neuhold
Loran Marie Killar
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 US08/994,689 external-priority patent/US6613958B1/en
Application filed by American Home Prod, Lisa Ann Neuhold, Loran Marie Killar filed Critical American Home Prod
Priority to IL13662698A priority Critical patent/IL136626A0/en
Priority to CA002314357A priority patent/CA2314357A1/en
Priority to JP2000524983A priority patent/JP2002533055A/en
Priority to AU19316/99A priority patent/AU1931699A/en
Priority to KR1020007006731A priority patent/KR100558288B1/en
Priority to EP98964125A priority patent/EP1040196A2/en
Publication of WO1999031969A2 publication Critical patent/WO1999031969A2/en
Publication of WO1999031969A3 publication Critical patent/WO1999031969A3/en
Priority to AU2003257928A priority patent/AU2003257928B2/en

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Classifications

    • 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
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489—Metalloendopeptidases (3.4.24)
    • C12N9/6491—Matrix metalloproteases [MMP's], e.g. interstitial collagenase (3.4.24.7); Stromelysins (3.4.24.17; 3.2.1.22); Matrilysin (3.4.24.23)
    • 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
    • A01K2217/00—Genetically modified animals
    • A01K2217/20—Animal model comprising regulated expression system
    • 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
    • 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
    • A01K2267/0393—Animal model comprising a reporter system for screening tests
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector 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)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Environmental Sciences (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Molecular Biology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Biochemistry (AREA)
  • Animal Husbandry (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention provides animal model systems for cartilage-degenerative disease, which comprise transgenic animals which can express recombinant matrix-degrading enzymes (MDEs), particularly matrix metalloproteinases (MMPs), in a temporally and spatially regulated manner. The invention also provides methods for producing phenotypic indicators of cartilage-degenerative disease in a mammal and methods for determining the potential of a composition to counteract cartilage-degenerative disease. The invention also provides isolated nucleic acids encoding proMMP polypeptides that exhibit constitutive enzymatic activity and isolated proMMP polypeptides.
PCT/US1998/027056 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage WO1999031969A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
IL13662698A IL136626A0 (en) 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage
CA002314357A CA2314357A1 (en) 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage
JP2000524983A JP2002533055A (en) 1997-12-19 1998-12-18 Transgenic animal model for cartilage degenerative disease
AU19316/99A AU1931699A (en) 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage
KR1020007006731A KR100558288B1 (en) 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage
EP98964125A EP1040196A2 (en) 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage
AU2003257928A AU2003257928B2 (en) 1997-12-19 2003-10-29 Transgenic animal model for degenerative diseases of cartilage

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US6831297P 1997-12-19 1997-12-19
US08/994,689 US6613958B1 (en) 1997-12-19 1997-12-19 Transgenic mouse model for degeneration of type II collagen in joints
US08/994,689 1997-12-19
US60/068,312 1997-12-19

Publications (2)

Publication Number Publication Date
WO1999031969A2 WO1999031969A2 (en) 1999-07-01
WO1999031969A3 true WO1999031969A3 (en) 1999-11-25

Family

ID=26748837

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/027056 WO1999031969A2 (en) 1997-12-19 1998-12-18 Transgenic animal model for degenerative diseases of cartilage

Country Status (8)

Country Link
EP (1) EP1040196A2 (en)
JP (1) JP2002533055A (en)
KR (2) KR100685105B1 (en)
AU (2) AU1931699A (en)
CA (1) CA2314357A1 (en)
CZ (1) CZ20002201A3 (en)
IL (1) IL136626A0 (en)
WO (1) WO1999031969A2 (en)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7005295B1 (en) 1997-04-16 2006-02-28 Wyeth β-amyloid peptide-binding proteins and polynucleotides encoding the same
US6787319B2 (en) 1997-04-16 2004-09-07 American Home Products Corp. β-amyloid peptide-binding proteins and polynucleotides encoding the same
US20040006205A1 (en) * 2001-04-03 2004-01-08 Li Li Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US6906036B2 (en) 2001-08-16 2005-06-14 Kimberly-Clark Worldwide, Inc. Anti-aging and wound healing compounds
US7071164B2 (en) 2001-08-16 2006-07-04 Kimberly-Clark Worldwide, Inc. Anti-cancer and wound healing compounds
US7186693B2 (en) 2001-08-16 2007-03-06 Kimberly - Clark Worldwide, Inc. Metalloproteinase inhibitors for wound healing
EP1469717A4 (en) * 2001-12-20 2007-08-22 Univ California TRIPLE TRANSGENIC MOUSE MODEL OF ALZHEIMER'S DISEASE
US7148194B2 (en) 2002-12-30 2006-12-12 Kimberly-Clark Worldwide, Inc. Method to increase fibronectin
US7189700B2 (en) 2003-06-20 2007-03-13 Kimberly-Clark Worldwide, Inc. Anti-chrondrosarcoma compounds
EP2024503A2 (en) * 2006-05-01 2009-02-18 Aarhus Universitet An animal model and a method for producing an animal model
KR20110025649A (en) 2008-05-05 2011-03-10 노비뮨 에스 에이 Anti-IL-173A / IL-173F cross-reactive antibody and method of use thereof
KR101811886B1 (en) 2009-05-05 2017-12-22 노비뮨 에스 에이 Anti-IL-17F Antibodies and Methods of Use Thereof
KR101176139B1 (en) * 2010-05-20 2012-08-22 광주과학기술원 Transgenic Mice Overexpressing HIF-2α as an Animal Model of Arthritis and Uses Thereof
JP6440148B2 (en) * 2013-12-12 2018-12-19 国立大学法人三重大学 Transgenic non-human mammal expressing human MMP2
KR102167443B1 (en) * 2019-03-25 2020-10-19 주식회사 카티프라임 In vitro osteoarthritis condition model and drug screening method for osteoarthritis using the same
WO2025176195A1 (en) * 2024-02-23 2025-08-28 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric mmp-7

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19501032A1 (en) * 1995-01-14 1996-07-18 Max Delbrueck Centrum Agent for treating rheumatic diseases esp. arthritis

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19501032A1 (en) * 1995-01-14 1996-07-18 Max Delbrueck Centrum Agent for treating rheumatic diseases esp. arthritis

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
D'ARMIENTO J ET AL: "Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema", CELL, vol. 71, 11 December 1992 (1992-12-11), pages 955 - 961, XP002105587 *
FREIJE J ET AL: "Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 269, no. 24, 17 June 1994 (1994-06-17), pages 16766 - 16773, XP002105588 *
KNÄUPER V ET AL: "Biochemical characterization of human collagenase-3", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 271, no. 3, 19 January 1996 (1996-01-19), pages 1544 - 1550, XP002105702 *
KNÄUPER V ET AL: "The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 272, no. 12, 21 March 1997 (1997-03-21), pages 7608 - 7616, XP002115522 *
KOZACI L ET AL: "Degradation of type II collagen, but not proteoglycan, correlates with matrix metalloproteinase activity in cartilage explant cultures", ARTHRITIS RHEUM, vol. 40, no. 1, January 1997 (1997-01-01), pages 164 - 174, XP002106784 *
SANCHEZ-LOPEZ R ET AL: "Structure-function relationships in the collagenase family member Transin", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 263, no. 24, 25 August 1988 (1988-08-25), pages 11892 - 11899, XP002105589 *
SHAPIRO SD: "Mighty mice: transgenic technology "knocks out" questions of matrix metalloproteinase function", MATRIX BIOLOGY, vol. 15, no. 8-9, March 1997 (1997-03-01), pages 527 - 533, XP002105138 *
SYMPSON C ET AL: "Targeted expression of stromelysin-1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression", J CELL BIOL., vol. 125, no. 3, May 1994 (1994-05-01), pages 681 - 693, XP002115516 *
WEIR E ET AL: "Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA., vol. 93, September 1996 (1996-09-01), pages 10240 - 10245, XP002105139 *

Also Published As

Publication number Publication date
KR20050109080A (en) 2005-11-17
KR100558288B1 (en) 2006-03-10
AU2003257928A1 (en) 2003-11-20
CA2314357A1 (en) 1999-07-01
JP2002533055A (en) 2002-10-08
KR100685105B1 (en) 2007-02-22
IL136626A0 (en) 2001-06-14
CZ20002201A3 (en) 2001-11-14
WO1999031969A2 (en) 1999-07-01
EP1040196A2 (en) 2000-10-04
KR20010033289A (en) 2001-04-25
AU2003257928B2 (en) 2007-07-12
AU1931699A (en) 1999-07-12

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