Wada E, Watase K, Yamada K, Ogura H, Yamano M, Inomata Y, Eguchi J, Yamamoto K, Sunday M E, Maeno H, Mikoshiba K, Ohki-Hamazaki H, Wada K
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, Tokyo, Japan.
Biochem Biophys Res Commun. 1997 Oct 9;239(1):28-33. doi: 10.1006/bbrc.1997.7418.
Gastrin-releasing peptide (GRP) is a mammalian bombesin-like peptide which is widely distributed in the central nervous system as well as in the gastrointestinal tract. GRP binds to its high affinity receptor (GRPR) to elicit a wide spectrum of biological effects on behavior, digestion, and metabolism. To define the in vivo function of GRPR, we generated GRPR null mutant mice by gene targeting. The intracerebroventricular administration of GRP caused hypothermia in wild-type mice, but not in mutant mice. The GRPR deficient mice showed significantly increased locomotor activity during the dark period, and social responses scored by sniffing, mounting, and approaching behaviors against an intruder. Aggressive scores such as fighting and biting were not altered in the mutant mice. These phenotypes were observed in mice generated from two independent ES cell clones and backcrossed to a C57BL/6J background. The GRPR deficient mice should be useful for studying the bombesin system in vivo.
胃泌素释放肽（GRP）是一种哺乳动物类铃蟾肽样肽，广泛分布于中枢神经系统以及胃肠道。GRP与其高亲和力受体（GRPR）结合，从而对行为、消化和代谢产生广泛的生物学效应。为了确定GRPR在体内的功能，我们通过基因打靶生成了GRPR基因敲除突变小鼠。向野生型小鼠脑室内注射GRP会导致体温过低，但突变小鼠则不会出现这种情况。GRPR缺陷型小鼠在黑暗期的自发活动显著增加，并且通过对入侵者的嗅探、爬跨和接近行为所记录的社交反应也增强。突变小鼠的攻击评分（如打斗和撕咬）没有改变。在来自两个独立胚胎干细胞克隆并回交至C57BL/6J背景的小鼠中观察到了这些表型。GRPR缺陷型小鼠将有助于在体内研究铃蟾肽系统。
