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

Abstract

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];  [1]
  1. Oak Ridge National Laboratory, Oak Ridge, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
75383
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 92; Journal Issue: 11; Other Information: PBD: 23 May 1995
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

Citation Formats

Klebig, M L, Woychik, R P, Wilkinson, J E, Geisler, J G, and Univ. of Tennessee, Knoxville, TN. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur. United States: N. p., 1995. Web. doi:10.1073/pnas.92.11.4728.
Klebig, M L, Woychik, R P, Wilkinson, J E, Geisler, J G, & Univ. of Tennessee, Knoxville, TN. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur. United States. https://doi.org/10.1073/pnas.92.11.4728
Klebig, M L, Woychik, R P, Wilkinson, J E, Geisler, J G, and Univ. of Tennessee, Knoxville, TN. 1995. "Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur". United States. https://doi.org/10.1073/pnas.92.11.4728.
@article{osti_75383,
title = {Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur},
author = {Klebig, M L and Woychik, R P and Wilkinson, J E and Geisler, J G and Univ. of Tennessee, Knoxville, TN},
abstractNote = {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.},
doi = {10.1073/pnas.92.11.4728},
url = {https://www.osti.gov/biblio/75383}, journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 11,
volume = 92,
place = {United States},
year = {Tue May 23 00:00:00 EDT 1995},
month = {Tue May 23 00:00:00 EDT 1995}
}