著者
柴田重信
所属
題材
生体リズム
被検体
マウス
データ収集方法
実験
専門分野
神経科学時間生物学遺伝学
評価指標
遺伝情報
キーワード
G-protein signalingRNA extractionthalamusmouse modelscircadian oscillatorscircadian rhythmsgene expressionPer2animal behavior
概要

書誌: PLoS ONE ,2011

PLoS ONE www.plosone.org  March 2011, Volume 6, Issue 3, e17655

Naoto Hayasaka, Kazuyuki Aoki, Saori Kinoshita, Shoutaroh Yamaguchi, John K. Wakefield,Sachiyo Tsuji-Kawahara, Kazumasa Horikawa, Hiroshi Ikegami, Shigeharu Wakana, Takamichi Murakami, Ram Ramabhadran, Masaaki Miyazawa, Shigenobu Shibata

Abstract Regulators of G protein signaling (RGS) are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs) of G protein a-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN), the master circadian lightentrainable oscillator (LEO) of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA) targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO)-driven elevated food-anticipatory activity (FAA) observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phaseadvanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s). 

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