Inactivation of Cipc alters the expression of Per1 but not circadian rhythms in mice.

Zhipeng Qu,Xiang Gao,Dongchuan Liu,Xiaohan Wang,Ying Xu

doi:10.1007/s11427-015-4828-1

Zhipeng Qu, Xiang Gao + Show 3 more

Open Access

https://doi.org/10.1007/s11427-015-4828-1

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Abstract

Circadian clocks are comprised of self-sustained transcriptional/translational feedback loops, which regulate the rhythms of physiology and behavior in mammals. CLOCK-interacting protein, Circadian (CIPC), has been indicated as an additional negative-feedback regulator of the circadian clock in vitro, although its physiological roles in circadian clock are unknown. Here, we generated Cipc homozygous knockout (Cipc (-/-)) mice and assessed the resultant circadian phenotypes. Surprisingly, the mRNA expression profiles of core clock genes in the liver of Cipc (-/-) mice showed no significant differences from that in wild-type mice except for Per1. Cipc (-/-) mice displayed normal locomotor rhythm and entrained activity pattern in both 12:12 light-dark cycle and constant dark cycle. Furthermore, deletion of Cipc in lungs and adipose tissues did not influence their peripheral clock. The results from this work provided more conclusive data suggesting that CIPC is not critically required for basic clock function.

Highlights

Circadian clocks generate circadian rhythms with a period about 24 h, and regulate the physiology and behavior of organisms to adapt to the light/dark cycle caused by rotation of the earth [1,2]
Previous studies identified a new regulator of circadian clock, CIPC, which interacts with CLOCK and represses the CLOCK-BMAL1-mediated transactivation by yeast twohybrid screening [9]
Since loss of CIPC has no notable effect on circadian rhythm of locomotor activity, which is organized by master clock in suprachiasmatic nuclei (SCN), we examined whether CIPC has a role in the peripheral clock

Summary

Introduction

Circadian clocks generate circadian rhythms with a period about 24 h, and regulate the physiology and behavior of organisms to adapt to the light/dark cycle caused by rotation of the earth [1,2]. Previous studies identified a new regulator of circadian clock, CIPC, which interacts with CLOCK and represses the CLOCK-BMAL1-mediated transactivation by yeast twohybrid screening [9]. Both knockdown of endogenous Cipc and overexpression of full length Cipc resulted in shorter circadian period lengths in fibroblast cells [9]. The expression of Per mRNA was decreased, Cipc mice retained normal circadian behavioral rhythms and displayed comparable extents of phase shift upon light stimulus. Our studies demonstrated that CIPC is dispensable for circadian clock

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