title: Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.
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 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).
authors.affiliation: Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. hayasaka@med.kindai.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Hayasaka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Aoki
authors.forename: Saori
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Shoutaroh
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: John K
authors.initials: JK
authors.lastname: Wakefield
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Tsuji-Kawahara
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Horikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.forename: Takamichi
authors.initials: T
authors.lastname: Murakami
authors.forename: Ram
authors.initials: R
authors.lastname: Ramabhadran
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D005247:Feeding Behavior / Q000502:physiology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism; D013997:Time Factors
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D020710:RGS Proteins; C107413:RGS16 protein; D012333:RNA, Messenger