Drug screens for regulators of the expression of the obese gene

Details Drug screens for regulators of the expression of the obese gene Drug screens for regulators of the expression of the obese gene

1996-09-04

1998-07-14

Degen, Nancy

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving viable micro-organism

435325, 435 8, 4351721, 4351723, 536 231, C12Q 102, C12Q 166, C12N 510, C12N 500

Patent

active

057802580

ABSTRACT:
The invention provides methods and compositions for screening for pharmacological agents which regulate satiety, fat metabolism and/or the type II diabetes mellitus in mammals, and in particular, agents active at regulating the level of ob gene expression. An exemplary assay involves (a) contacting a mammalian adipocyte comprising a mutant of a native ob allele encoding a reporter of ob gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native ob allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates ob gene expression. Preferred methods include cell-based transcription assays using adipocytes from transgenic animals having a "knock-in" luciferase reporter at least one ob allele.

REFERENCES:
Gong, et al., 1996, Journal of Biological Chemistry, vol. 271., No. 8, pp. 3971-3974.
Miller, et al. 1996. PNAS. vol. 93 pp. 5507-5511.
Mansour, et al. 1990 PNAS vol. 87 pp. 7688-7692.

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