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Title: Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur

Mice that carry the lethal yellow (A{sup y}) or viable yellow (A{sup vy}) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant {open_quotes}obese yellow{close_quotes} a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants. 42 refs., 5 figs.
Authors:
;  [1] ;  [2] ;  [3]
  1. Oak Ridge National Laboratory, Oak Ridge, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
  3. Oak Ridge National Laboratory, Oak Ridge, TN (United States)|[Univ. of Tennessee, Knoxville, TN (United States)
Publication Date:
OSTI Identifier:
75383
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; Journal Volume: 92; Journal Issue: 11; Other Information: PBD: 23 May 1995
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; TRANSGENIC MICE; DOMINANT MUTATIONS; PHENOTYPE; HAIR; GENETIC CONTROL; NEOPLASMS; DIABETES MELLITUS