Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in RGS16 knockdown mice

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Regulators of G protein signaling (RGS) are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs) of G protein α-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 light-entrainable 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 phase-advanced 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).

Original languageEnglish
Article numbere17655
JournalPloS one
Issue number3
Publication statusPublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General


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