Loss of prokineticin receptor 2 signaling predisposes mice to torpor.

Loss of prokineticin receptor 2 signaling predisposes mice to torpor.
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DOI:
10.1152/ajpregu.00778.2007
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发表时间:
2008-06
期刊:
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子:
--
通讯作者:
Ebling FJ
Ebling FJ
中科院分区:
其他
文献类型:
--
作者:
Jethwa PH;I'Anson H;Warner A;Prosser HM;Hastings MH;Maywood ES;Ebling FJ

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编码前动力蛋白2多肽(Prok 2)及其同源受体(Prokr 2/Gpcr 73 l1)的基因广泛表达于视交叉上核(SCN)及其下丘脑靶区,该信号通路参与了行为和生理的昼夜节律调节。我们先前已经观察到,Prokr 2的靶向无效突变破坏了运动活动和体温调节周期的昼夜协调。我们现在已经在大多数缺乏Prokr 2信号转导的转基因小鼠中观察到自发但零星的麻痹发作。在这些持续长达8小时的麻痹发作期间,体温和自主活动明显下降。耗氧量和二氧化碳的产生也有所下降,RQ也有所下降。当小鼠维持12:12的明-暗周期时,这些自发性麻痹发作通常在黑暗期结束或光照期早期开始,并在小鼠暴露于持续黑暗时持续存在。食物剥夺的时间(16- 24小时)在所有小鼠中诱导体温大幅下降,但与杂合和野生型同窝小鼠相比,缺乏Prokr 2信号传导的小鼠中体温过低的持续时间和深度显著更大。同样,当在代谢笼中进行测试时,与对照组相比,食物剥夺使转基因小鼠的耗氧量和二氧化碳产生量大幅下降。我们的结论是,Prokr 2信号在下丘脑调节能量平衡中起着重要作用,该途径的丧失导致通常仅在小鼠处于负能量平衡时才能检测到的生理和行为反应。
The genes encoding prokineticin 2 polypeptide (Prok2) and its cognate receptor (Prokr2/Gpcr73l1) are widely expressed in both the suprachiasmatic nucleus (SCN) and its hypothalamic targets, and this signaling pathway has been implicated in the circadian regulation of behavior and physiology. We have previously observed that the targeted null mutation of Prokr2 disrupts circadian co-ordination of cycles of locomotor activity and thermoregulation. We have now observed spontaneous but sporadic bouts of torpor in the majority of these transgenic mice lacking Prokr2 signaling. During these torpor bouts, which lasted for up to 8h, body temperature and locomotor activity decreased markedly. Oxygen consumption and carbon dioxide production also decreased, and there was a decrease in RQ. These spontaneous torpor bouts generally began towards the end of the dark phase or in the early light phase when the mice were maintained on a 12:12 light-dark cycle, and persisted when mice were exposed to continuous darkness. Periods of food deprivation (16-24h) induced a substantial decrease in body temperature in all mice, but the duration and depth of hypothermia was significantly greater in mice lacking Prokr2 signaling compared to heterozygous and wild-type litter mates. Likewise, when tested in metabolic cages, food deprivation produced greater decreases in oxygen consumption and carbon dioxide production in the transgenic mice than the controls. We conclude that Prokr2 signaling plays a role in the hypothalamic regulation of energy balance, and loss of this pathway results in physiological and behavioral responses normally only detected when mice are in negative energy balance.
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