Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity

Nature. 1997 Nov 13;390(6656):165-9. doi: 10.1038/36568.


Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Blood Pressure
  • Body Weight
  • Energy Metabolism
  • Female
  • Gene Deletion
  • Gene Targeting
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Heart Rate
  • Hormones / blood
  • Leptin
  • Male
  • Metabolic Diseases / blood
  • Metabolic Diseases / etiology*
  • Mice
  • Mice, Inbred ICR
  • Motor Activity
  • Obesity / blood
  • Obesity / etiology*
  • Proteins / metabolism
  • Receptors, Bombesin / deficiency
  • Receptors, Bombesin / genetics
  • Receptors, Bombesin / physiology*


  • Hormones
  • Leptin
  • Proteins
  • Receptors, Bombesin
  • bombesin receptor subtype 3
  • Glucose