Claims
- 1. A method of screening for an inhibitor of acetyl-CoA carboxylase 2 isoform activity, comprising the steps of:administering a potential inhibitor to one or more wild type mouse; and screening said one or more mouse for a phenotype exhibited by a transgenic mouse whose genome comprises a homozygous disruption of an endogenous ACC2 gene for the acetyl-CoA carboxylase 2 isoform of acetyl-CoA carboxylase, wherein said disruption inactivates said gene and wherein said mouse does not produce any functional acetyl-CoA carboxylase 2, selecting the inhibitor when given to a wild type mouse whose phenotype is exhibited the same as that of the transgenic mouse.
- 2. The method of claim 1, wherein said phenotype comprises:a metabolic reduction in malonyl-CoA production in skeletal muscle and heart; unrestricted fat oxidation and reduced fat accumulation in the liver and fat storage cells; and consuming more calories yet accumulating less fat than said one or more wild type mouse.
- 3. The method of claim 1, wherein one or more exons of said ACC2 gene has been deleted.
- 4. The method of claim 3, wherein said exon(s) have been replaced with heterologous DNA sequences.
- 5. The method of claim 4, wherein said heterologous DNA sequences comprise a hypoxanthine phosphorylribosyltransferase expression cassette.
- 6. The method of claim 5, wherein an exon encoding a biotin binding motif of ACC2 is replaced with an a hypoxanthine phosphorylribosyltransferase expression cassette.
CROSS-REFERENCE TO RELATED APPLICATION
This non-provisional patent application is a continuation in part of, claims benefit of, U.S. Ser. No. 09/749,109, filed Dec. 26, 2000 now U.S. Pat. No. 6,548,738.
FEDERAL FUNDING LEGEND
This invention was produced in part using funds from the Federal government under N.I.H. G.M. 19091. Accordingly, the Federal government has certain rights in this invention.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
6258547 |
Beri et al. |
Jul 2001 |
B1 |
6485941 |
Waldrop |
Nov 2002 |
B1 |
Non-Patent Literature Citations (5)
Entry |
Moens et al. Defects in heart and lung development in compound heterozygotes for two different targeted mutations at the N-myc locus, Development, 1993, vol. 119, pp. 485-499.* |
Moreadith et al. Gene targeting in embryonic stem cells: the new physiology and metabolism, Journal of Molecular Medicine, 1997, vol. 75, pp. 208-216.* |
Abu-Elheiga, et al. The Subcellular Localization of Acetyl-COA Carboxylase 2. PNAS, vol. 97, 2000, pp. 1444-1449. |
Munday, et al. The Regulation of Acetyl-COA Carboxylase—A Potential Target for the Action of Hypolipidemic Agents. Advan. Enzyme Regul., vol. 39, 1999, pp. 205-234. |
Abu-Elheiga, et al. Human Acetyl-COA Carboxylase 2. J. of Biological Chemistry, vol. 272, 1997, pp. 10669-10677. |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09/749109 |
Dec 2000 |
US |
Child |
09/929575 |
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US |