Progress in FY2015 includes the following: In order to study the specific cells, sites, tissues, and transmitters by which BRS-3 acts, we have generated floxed Brs3 mouse. The floxed mice allow determination of necessity of Brs3 in the particular cells. We are in the process of using this mouse by breeding with germline cre-expressing mice and by injection of cre-expressing virus into specific brain nuclei. These allow knockout of Brs3 in cells defined by their cre expression pattern or by location within the brain. Similarly, we have generated loxTB-Brs3 mice. The loxTB-Brs3 mice allow determination of sufficiency of Brs3 in the particular cells. We have achieved germline transmission and are expanding the line and in the process of proving that the mice have the expected characteristics. These mice allow expression of Brs3 only in cells defined by their cre expression pattern and by location within the brain. Finally we have generated Brs3-T2A-CreERT2 mice, in which cre is expressed as a fusion mRNA with the endogenous Brs3 mRNA, leading to cre protein expression expected to be at similar level as Brs3. We have now shown that these mice do express cre in a tamoxifen-dependent manner and in the reported distribution pattern of Brs3. We are expanding the line.

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5
Fiscal Year
2015
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U.S. National Inst Diabetes/Digst/Kidney
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Xiao, Cuiying; Piñol, Ramón A; Carlin, Jesse Lea et al. (2018) Corrigendum to ""Bombesin-like receptor 3 (Brs3) expression in glutamatergic, but not GABAergic, neurons is required for regulation of energy metabolism"" [Mol Metabol 6 (2017) 1540-1550]. Mol Metab 9:220
Piñol, Ramón A; Zahler, Sebastian H; Li, Chia et al. (2018) Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake. Nat Neurosci 21:1530-1540
Xiao, Cuiying; Reitman, Marc L (2016) Bombesin-Like Receptor 3: Physiology of a Functional Orphan. Trends Endocrinol Metab 27:603-605
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Lateef, Dalya M; Xiao, Cuiying; Reitman, Marc L (2015) Search for an Endogenous Bombesin-Like Receptor 3 (BRS-3) Ligand Using Parabiotic Mice. PLoS One 10:e0142637
Lateef, Dalya M; Abreu-Vieira, Gustavo; Xiao, Cuiying et al. (2014) Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3. Am J Physiol Endocrinol Metab 306:E681-7
Hatoum, Ida J; Greenawalt, Danielle M; Cotsapas, Chris et al. (2013) Weight loss after gastric bypass is associated with a variant at 15q26.1. Am J Hum Genet 92:827-34
Moreno, Paola; Mantey, Samuel A; Nuche-Berenguer, Bernardo et al. (2013) Comparative pharmacology of bombesin receptor subtype-3, nonpeptide agonist MK-5046, a universal peptide agonist, and peptide antagonist Bantag-1 for human bombesin receptors. J Pharmacol Exp Ther 347:100-16
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Chobanian, Harry R; Guo, Yan; Liu, Ping et al. (2012) The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization. Bioorg Med Chem 20:2845-9

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