A new mammalian circadian oscillator model including the cAMP module
Wang Jun-Wei(王军威)a)† and Zhou Tian-Shou(周天寿)b)
a School of Informatics, Guangdong University of Foreign Studies, Guangzhou 510006, China; b School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou 510275, China
Abstract In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops (TTFLs) and a cAMP-mediated feedback loop. The model shows that TTFLs and cAMP signalling cooperatively drive the circadian rhythms. It reproduces typical experimental observations with qualitative similarities, e.g. circadian oscillations in constant darkness and entrainment to light--dark cycles. In addition, it can explain the phenotypes of cAMP-mutant and Rev-erb$\alpha$-/- -mutant mice, and help us make an experimentally-testable prediction: oscillations may be rescued when arrhythmic mice with constitutively low concentrations of cAMP are crossed with Rev-erb$\alpha$-/- mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell.
Received: 30 March 2009
Revised: 28 April 2009
Accepted manuscript online:
Fund: Project supported by the State Key
Program of National Natural Science Foundation of China (Grant No
60736028), the National Natural Science Foundation of China (Grant
Nos 10871074 and 60704045), and the Research Fund for the Doctoral
Program of Higher Ed
Cite this article:
Wang Jun-Wei(王军威) and Zhou Tian-Shou(周天寿) A new mammalian circadian oscillator model including the cAMP module 2009 Chin. Phys. B 18 5552
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