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

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(1). 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)(2,3), neuromedin B receptor (NMB-R)(4,5), and bombesin receptor subtype-3 (BRS-3)(6,7). 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.