Targeted disruption of the melanocortin-4 receptor results in obesity in mice

Dennis Huszar, Catherine A. Lynch, Victoria Fairchild-Huntress, Judy H. Dunmore, Qing Fang, Lucy R. Berkemeier, Wei Gu, Robert A. Kesterson, Bruce A. Boston, Roger D. Cone, Francoise J. Smith, L. Arthur Campfield, Paul Burn, Lee Frank

Research output: Contribution to journalArticle

2322 Scopus citations

Abstract

The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven- transmembrane receptor expressed in the brain. Inactivation of this receptor by gene targeting results in mice that develop a maturity onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates several of the characteristic features of the agouti obesity syndrome, which results from ectopic expression of agouti protein, a pigmentation factor normally expressed in the skin. Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.

Original languageEnglish (US)
Pages (from-to)131-141
Number of pages11
JournalCell
Volume88
Issue number1
DOIs
StatePublished - Jan 10 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., Smith, F. J., Campfield, L. A., Burn, P., & Frank, L. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 88(1), 131-141. https://doi.org/10.1016/S0092-8674(00)81865-6