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 behaviour1. 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.
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We thank J.-I. Miyazaki for ES cells and training regarding ES cells; A. F. Parlow for mouse growth hormone and polyclonal monkey anti-rat GH serum; K. Wakabayashi for goat anti-monkey IgG serum; H. Ohno for rat UCP1 probe; T. Nishikawa for providing Animex Auto; N. M. Le Douarin, K. Mikoshiba, R. S. Petralia and J. Smith for critical reading of the manuscript. This work was supported in part by research grants from the Ministry of Education, Science, Sports and Culture, the Ministry of Health and Welfare, the Science and Technology Agency of Japan, the Japan Health Science Foundation.
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Ohki-Hamazaki, H., Watase, K., Yamamoto, K. et al. Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature 390, 165–169 (1997). https://doi.org/10.1038/36568
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