Title:
NON-HUMAN TRANSGENIC ANIMAL WHOSE GERM CELLS AND SOMATIC CELLS CONTAIN A KNOCKOUT MUTATION IN DNA ENCODING ORPHAN NUCLEAR RECEPTOR ERRalpha
Document Type and Number:
WIPO Patent Application WO2000047735
Kind Code:
A3
Abstract:
The present invention relates to a transgenic non-human mammal whose germ cells and somatic cells contain a knockout mutation in DNA encoding orphan nuclear receptor ERR alpha . More specifically, the invention relates to knockout mice whose germ cells and somatic cells contain a knockout mutation in DNA encoding orphan nuclear receptor ERR alpha . The invention further relates to such knockout non-human mammals which express an ERR alpha gene which is different from the endogenous gene which was disrupted. In a particular embodiment, the invention relates to a transgenic mouse having its endogenous ERR alpha gene disrupted and expressing human ERR alpha . As well, the invention relates to cell lines in which ERR alpha activity (and/or level) has been inactivated or augmented. The invention further relates to uses and methods of the transgenic animals of the present invention to select agents which modulate the expression and/or activity of ERR alpha , in particular in relation to fatty acid metabolism.
Inventors:
GIGUERE VINCENT (CA)
SLADEK ROBERT (CA)
LUO JIANG-MING (US)
SLADEK ROBERT (CA)
LUO JIANG-MING (US)
Application Number:
PCT/CA2000/000145
Publication Date:
November 30, 2000
Filing Date:
February 08, 2000
Export Citation:
Assignee:
UNIV MCGILL (CA)
GIGUERE VINCENT (CA)
SLADEK ROBERT (CA)
LUO JIANG MING (US)
GIGUERE VINCENT (CA)
SLADEK ROBERT (CA)
LUO JIANG MING (US)
International Classes:
A61P3/06; C07K14/705; C12N15/12; C12N15/85; A61K38/00; A61K48/00; (IPC1-7): C12N15/12; A01K67/027; A61K39/395; A61K48/00; A61K49/00; A61P3/06; C07K14/705; C12N5/10; C12N15/11; C12Q1/68; G01N33/50
Domestic Patent References:
| WO1999065486A1 | 1999-12-23 |
Foreign References:
| EP0733705A1 | 1996-09-25 |
Other References:
BRYANT H AND DERE W: "Selective estrogen receptor modulators: an alternative to hormone replacement therapy", PROC SOC EXP BIOL MED., vol. 217, no. 1, January 1998 (1998-01-01), pages 45 - 52, XP002142941
SLADEK R ET AL: "The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene", MOL CELL BIOL., vol. 17, no. 9, September 1997 (1997-09-01), pages 5400 - 5409, XP002142942
VEGA R ET AL: "A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 272, no. 50, 12 December 1997 (1997-12-12), pages 31693 - 31699, XP002142943
LUO J ET AL: "Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta", NATURE., vol. 388, no. 6644, 21 August 1997 (1997-08-21), pages 778 - 782, XP002142944
SLADEK R ET AL: "The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene", MOL CELL BIOL., vol. 17, no. 9, September 1997 (1997-09-01), pages 5400 - 5409, XP002142942
VEGA R ET AL: "A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 272, no. 50, 12 December 1997 (1997-12-12), pages 31693 - 31699, XP002142943
LUO J ET AL: "Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta", NATURE., vol. 388, no. 6644, 21 August 1997 (1997-08-21), pages 778 - 782, XP002142944
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