WO2002028175A3 - Transgenic mouse for targeted recombination mediated by modified cre-er - Google Patents

Transgenic mouse for targeted recombination mediated by modified cre-er Download PDF

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Publication number
WO2002028175A3
WO2002028175A3 PCT/IB2001/002246 IB0102246W WO0228175A3 WO 2002028175 A3 WO2002028175 A3 WO 2002028175A3 IB 0102246 W IB0102246 W IB 0102246W WO 0228175 A3 WO0228175 A3 WO 0228175A3
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WIPO (PCT)
Prior art keywords
organism
interest
recombinase
transgenic mouse
targeted recombination
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Application number
PCT/IB2001/002246
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French (fr)
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WO2002028175A9 (en
WO2002028175A2 (en
Inventor
Pierre Chambon
Daniel Metzger
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Ass Pour Le Dev De La Rech
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Publication date
Priority claimed from FR0012570A external-priority patent/FR2814642B1/en
Application filed by Ass Pour Le Dev De La Rech filed Critical Ass Pour Le Dev De La Rech
Priority to EP01986247A priority Critical patent/EP1322152A2/en
Publication of WO2002028175A2 publication Critical patent/WO2002028175A2/en
Publication of WO2002028175A3 publication Critical patent/WO2002028175A3/en
Publication of WO2002028175A9 publication Critical patent/WO2002028175A9/en

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    • 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
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    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
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    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
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    • 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
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    • A01K2217/00—Genetically modified animals
    • A01K2217/20—Animal model comprising regulated expression system
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    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2267/03—Animal model, e.g. for test or diseases
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    • 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
    • A01K2267/0331—Animal model for proliferative diseases
    • 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
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0362—Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
    • 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
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0368—Animal model for inflammation
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    • C07—ORGANIC CHEMISTRY
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    • C07K2319/00—Fusion polypeptide
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    • 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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    • C12N2830/00—Vector systems having a special element relevant for transcription
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    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
    • C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian

Abstract

The present invention relates to a metazoan organism, with the exception of humans, and in particular a mouse, characterized in that at least one cell of this organism comprises at least one fusion protein between a recombinase Cre and a modified ligand binding domain of the nuclear estrogen receptor alpha, allowing the inactive fused recombinase to be induced by synthetic antiestrogens, but not by natural estrogens, and one or more DNA sequences of interest belonging to the genome of said organism into which one or more sites of recognition of said recombinase protein are inserted. The invention also covers the methods using said organism for the screening of medicaments, the mutagenesis and the analysis of the biological function of the DNA sequence(s) of interest, in particular of gene(s) of interest, such as RXRα.
PCT/IB2001/002246 2000-10-03 2001-09-28 Transgenic mouse for targeted recombination mediated by modified cre-er WO2002028175A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP01986247A EP1322152A2 (en) 2000-10-03 2001-09-28 Transgenic mouse for targeted recombination mediated by modified cre-er

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR0012570A FR2814642B1 (en) 2000-10-03 2000-10-03 TRANSGENIC MOUSE FOR THE TARGETED RECOMBINATION MEDIATED BY THE MODIFIED CRE-ER
FR00/12570 2000-10-03
US09/853,033 2001-05-11
US09/853,033 US7112715B2 (en) 2000-10-03 2001-05-11 Transgenic mouse for targeted recombination mediated by modified Cre-ER

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WO2002028175A2 WO2002028175A2 (en) 2002-04-11
WO2002028175A3 true WO2002028175A3 (en) 2003-01-09
WO2002028175A9 WO2002028175A9 (en) 2003-10-30

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JP2007535906A (en) * 2003-10-24 2007-12-13 イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー Orthogonal gene switch
CN100387722C (en) * 2004-02-18 2008-05-14 中国人民解放军军事医学科学院生物工程研究所 Method for preparing transgenic mouse with central nervous system specific expression Cre recombinase
US20080184380A1 (en) * 2004-10-22 2008-07-31 Therapeutic Human Polyclonals Inc. Suppression of Endogenous Immunoglobulin Expression in Non-Human Transgenic Animals
EP2067858A1 (en) 2007-12-07 2009-06-10 Universidad de Sevilla Animal models for neurodegenerative diseases
ES2337973B8 (en) 2008-05-16 2011-07-21 Proyecto De Biomedicina Cima, S.L. ADENOVIRUS AUXILIARY SELF-INACTIVANTS FOR THE PRODUCTION OF ADENOVIRUS RECOMBINANTS OF HIGH CAPACITY.
WO2018129203A2 (en) * 2017-01-06 2018-07-12 The Regents Of The University Of California Method for temporal and tissue-specific drug delivery and induced nucleic acid recombination
CN112921052B (en) * 2019-12-06 2023-07-21 中国科学院分子细胞科学卓越创新中心 In vivo cell proliferation marker and tracer system and application thereof

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992006104A1 (en) * 1990-09-28 1992-04-16 The Dana-Farber Cancer Institute Adipocyte-specific dna sequences and use for the production of transgenic animals exhibiting altered fat metabolism
WO1994026100A1 (en) * 1993-05-18 1994-11-24 Institut National De La Sante Et De La Recherche Medicale Genetically engineered mice containing alterations in the genes encoding retinoic acid receptor proteins
WO1995000555A1 (en) * 1993-06-28 1995-01-05 European Molecular Biology Laboratory (Embl) Regulation of site-specific recombination by site-specific recombinase/nuclear receptor fusion proteins
EP0698392A1 (en) * 1994-08-02 1996-02-28 L'oreal Compositions containing a RAR alpha specific ligand and at least one fatty acid
WO1997010819A1 (en) * 1995-09-18 1997-03-27 Ligand Pharmaceuticals Incorporated Treating niddm with rxr agonists
WO1997031108A1 (en) * 1996-02-20 1997-08-28 Association Pour Le Developpement De La Recherche En Genetique Moleculaire (Aderegem) Modified nuclear glucocorticoid receptor, fusion protein, and dna fragments coding for said receptor and said fusion protein
WO1999018222A1 (en) * 1997-10-08 1999-04-15 Pharmacia & Upjohn Ab Use of beta recombinase in eukaryotic cells, especially for transgenic work
WO1999025851A1 (en) * 1997-11-13 1999-05-27 Sumitomo Pharmaceuticals Company, Limited VARIANT loxP SEQUENCES AND APPLICATION OF THE SAME
US6093873A (en) * 1996-08-19 2000-07-25 Institut National De La Sante Et De La Recherche Medicale Genetically engineered mice containing alterations in the gene encoding RXR
WO2000049147A1 (en) * 1999-02-19 2000-08-24 Octagene Gmbh Hormone-hormone receptor complexes and nucleic acid constructs and their use in gene therapy

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992006104A1 (en) * 1990-09-28 1992-04-16 The Dana-Farber Cancer Institute Adipocyte-specific dna sequences and use for the production of transgenic animals exhibiting altered fat metabolism
WO1994026100A1 (en) * 1993-05-18 1994-11-24 Institut National De La Sante Et De La Recherche Medicale Genetically engineered mice containing alterations in the genes encoding retinoic acid receptor proteins
WO1995000555A1 (en) * 1993-06-28 1995-01-05 European Molecular Biology Laboratory (Embl) Regulation of site-specific recombination by site-specific recombinase/nuclear receptor fusion proteins
EP0698392A1 (en) * 1994-08-02 1996-02-28 L'oreal Compositions containing a RAR alpha specific ligand and at least one fatty acid
WO1997010819A1 (en) * 1995-09-18 1997-03-27 Ligand Pharmaceuticals Incorporated Treating niddm with rxr agonists
WO1997031108A1 (en) * 1996-02-20 1997-08-28 Association Pour Le Developpement De La Recherche En Genetique Moleculaire (Aderegem) Modified nuclear glucocorticoid receptor, fusion protein, and dna fragments coding for said receptor and said fusion protein
US6093873A (en) * 1996-08-19 2000-07-25 Institut National De La Sante Et De La Recherche Medicale Genetically engineered mice containing alterations in the gene encoding RXR
WO1999018222A1 (en) * 1997-10-08 1999-04-15 Pharmacia & Upjohn Ab Use of beta recombinase in eukaryotic cells, especially for transgenic work
WO1999025851A1 (en) * 1997-11-13 1999-05-27 Sumitomo Pharmaceuticals Company, Limited VARIANT loxP SEQUENCES AND APPLICATION OF THE SAME
WO2000049147A1 (en) * 1999-02-19 2000-08-24 Octagene Gmbh Hormone-hormone receptor complexes and nucleic acid constructs and their use in gene therapy

Non-Patent Citations (17)

* Cited by examiner, † Cited by third party
Title
BARLOW C ET AL: "Targeted expression of Cre recombinase to adipose tissue of transgenic mice directs adipose-specific excision of loxP-flanked gene segments", NUCLEIC ACIDS RESEARCH., vol. 25, no. 12, 1997, pages 2543 - 2545, XP002200980 *
DATABASE GENESEQ [online] 3 August 1999 (1999-08-03), STEWART F: "SSR-LBD Fusion Polypeptide", XP002175669, retrieved from E.B.I. HINXTON G.B. Database accession no. AAY21544 *
FEIL R ET AL: "Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS., vol. 237, no. 3, 28 August 1997 (1997-08-28), pages 752 - 757, XP002144708 *
FENG X ET AL: "Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse epidermis impairs regulation of gene transcription and basal keratinocyte proliferation by RAR-selective retinoids", GENES & DEVELOPMENT, vol. 11, no. 1, 1997, pages 59 - 71, XP001016150 *
IMAI T ET AL: "Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA., vol. 98, no. 1, 2 January 2001 (2001-01-02), pages 224 - 228, XP002200981 *
IMAI T ET AL: "INDUCIBLE SITE-SPECIFIC SOMATIC MUTAGENESIS IN MOUSE HEPATOCYTES", GENESIS, WILEY-LISS, NEW YORK, NY,, US, no. 2, February 2000 (2000-02-01), pages 147 - 148, XP001006343, ISSN: 1526-954X *
INDRA A ET AL: "Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases", NUCLEIC ACIDS RESEARCH, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 27, no. 22, 15 November 1999 (1999-11-15), pages 4324 - 4327, XP002144711, ISSN: 0305-1048 *
KASTNER P ET AL: "Vitamin A deficiency and mutations of RXRalpha, RXRbeta and RARalpha lead to early differentiation of embryonic ventricular cardiomyocytes", DEVELOPMENT, vol. 124, no. 23, December 1997 (1997-12-01), pages 4749 - 4758, XP002175667 *
LI M ET AL: "Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis", NATURE, vol. 407, no. 6804, 5 October 2000 (2000-10-05), pages 633 - 636, XP002200979 *
MAHFOUDI ABDERRAHIM ET AL: "Specific mutations in the estrogen receptor change the properties of antiestrogens to full agonists.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 92, no. 10, 1995, 1995, pages 4206 - 4210, XP002200983, ISSN: 0027-8424 *
METZGER D ET AL: "CONDITIONAL SITE-SPECIFIC RECOMBINATION IN MAMMALIAN CELLS USING A LIGAND-DEPENDENT CHIMERIC CRE RECOMBINASE", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 92, no. 15, 18 July 1995 (1995-07-18), pages 6991 - 6995, XP002022517, ISSN: 0027-8424 *
METZGER D ET AL: "ENGINEERING THE MOUSE GENOME BY SITE-SPECIFIC RECOMBINATION", CURRENT OPINION IN BIOTECHNOLOGY, LONDON, GB, vol. 10, no. 5, October 1999 (1999-10-01), pages 470 - 476, XP001004690, ISSN: 0958-1669 *
RAGHAVAN S ET AL: "Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination", THE JOURNAL OF CELL BIOLOGY., vol. 150, no. 5, 4 September 2000 (2000-09-04), pages 1149 - 1160, XP002175666 *
SALTOU M ET AL: "INHIBITION OF SKIN DEVELOPMENT BY TARGETED EXPRESSION OF A DOMINANT-NEGATIVE RETINOIC ACID RECEPTOR", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 374, 9 March 1995 (1995-03-09), pages 159 - 162, XP000573887, ISSN: 0028-0836 *
SUMI-ICHINOSE C ET AL: "SNF2beta-BRG1 is essential for the viability of F9 murine embryonal carcinoma cells", MOL CELL BIOL, vol. 17, no. 10, October 1997 (1997-10-01), pages 5976 - 5986, XP002175668 *
VASIOUKHIN V ET AL: "The magical touch: Genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA., vol. 96, no. 15, 20 July 1999 (1999-07-20), pages 8551 - 8556, XP002144707 *
WAN Y ET AL: "Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver", MOL CELL BIOL, vol. 20, no. 12, June 2000 (2000-06-01), pages 4436 - 4444, XP002200982 *

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