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

Cell. 1997 Jan 10;88(1):131-41. doi: 10.1016/s0092-8674(00)81865-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Brain Chemistry
  • Disease Models, Animal
  • Eating
  • Female
  • Gene Expression
  • Gene Targeting / methods*
  • Heterozygote
  • Homozygote
  • Insulin / blood
  • Leptin
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Obesity / blood
  • Obesity / genetics*
  • Pro-Opiomelanocortin / genetics
  • Proteins / analysis
  • RNA, Messenger / analysis
  • Receptor, Melanocortin, Type 4
  • Receptors, Peptide / genetics
  • Receptors, Peptide / physiology*
  • Signal Transduction
  • Weight Gain / genetics

Substances

  • Blood Glucose
  • Insulin
  • Leptin
  • Proteins
  • RNA, Messenger
  • Receptor, Melanocortin, Type 4
  • Receptors, Peptide
  • Pro-Opiomelanocortin