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Science 3 October 1997:
Vol. 278. no. 5335, pp. 135 - 138
DOI: 10.1126/science.278.5335.135
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Reports

Antagonism of Central Melanocortin Receptors in Vitro and in Vivo by Agouti-Related Protein

Michael M. Ollmann, * Brent D. Wilson, * Ying-Kui Yang, Julie A. Kerns, Yanru Chen, Ira Gantz, Gregory S. Barsh dagger

Expression of Agouti protein is normally limited to the skin where it affects pigmentation, but ubiquitous expression causes obesity. An expressed sequence tag was identified that encodes Agouti-related protein, whose RNA is normally expressed in the hypothalamus and whose levels were increased eightfold in ob/ob mice. Recombinant Agouti-related protein was a potent, selective antagonist of Mc3r and Mc4r, melanocortin receptor subtypes implicated in weight regulation. Ubiquitous expression of human AGRP complementary DNA in transgenic mice caused obesity without altering pigmentation. Thus, Agouti-related protein is a neuropeptide implicated in the normal control of body weight downstream of leptin signaling.

M. M. Ollmann, B. D. Wilson, J. A. Kerns, Y. Chen, G. S. Barsh, Departments of Pediatrics and Genetics and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Y.-K. Yang and I. Gantz, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109-0682, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed at Beckman Center B271A, Stanford University School of Medicine, Stanford, CA 94305-5323, USA. E-mail: gbarsh{at}cmgm.stanford.edu.

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