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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Dunlap JC. Molecular bases for circadian clocks. Cell, 1999, 96: 271–290
Bass J, Takahashi JS. Circadian integration of metabolism and energetics. Science, 2010, 330: 1349–1354
Lowrey PL, Takahashi JS. Genetics of circadian rhythms in mammalian model organisms. Adv Genet, 2011, 74: 175–230
King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL, Turek FW, Takahashi JS. Positional cloning of the mouse circadian clock gene. Cell, 1997, 89: 641–653
Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ. Role of the clock protein in the mammalian circadian mechanism. Science, 1998, 280: 1564–1569
Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U. The orphan nuclear receptor rev-erbalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell, 2002, 110: 251–260
Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA, Hogenesch JB. A functional genomics strategy reveals rora as a component of the mammalian circadian clock. Neuron, 2004, 43: 527–537
Cho H, Zhao X, Hatori M, Yu RT, Barish GD, Lam MT, Chong LW, DiTacchio L, Atkins AR, Glass CK, Liddle C, Auwerx J, Downes M, Panda S, Evans RM. Regulation of circadian behaviour and metabolism by REV-ERB-alpha and REV-ERB-beta. Nature, 2012, 485: 123–127
Zhao WN, Malinin N, Yang FC, Staknis D, Gekakis N, Maier B, Reischl S, Kramer A, Weitz CJ. Cipc is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol, 2007, 9: 268–275
Xu Y, Toh KL, Jones CR, Shin JY, Fu YH, Ptacek LJ. Modeling of a human circadian mutation yields insights into clock regulation by per2. Cell, 2007, 128: 59–70
Wang X, Tang J, Xing L, Shi G, Ruan H, Gu X, Liu Z, Wu X, Gao X, Xu Y. Interaction of MAGED1 with nuclear receptors affects circadian clock function. EMBO J, 2010, 29: 1389–1400
Yamazaki S, Takahashi JS. Real-time luminescence reporting of circadian gene expression in mammals. Methods Enzymol, 2005, 393: 288–301
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at springerlink.fh-diploma.de
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Qu, Z., Wang, X., Liu, D. et al. Inactivation of Cipc alters the expression of Per1 but not circadian rhythms in mice. Sci. China Life Sci. 58, 368–372 (2015). https://doi.org/10.1007/s11427-015-4828-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-015-4828-1