中国物理B ›› 2009, Vol. 18 ›› Issue (12): 5552-5559.doi: 10.1088/1674-1056/18/12/070

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A new mammalian circadian oscillator model including the Camp module

王军威1, 周天寿2   

  1. (1)School of Informatics, Guangdong University of Foreign Studies, Guangzhou 510006, China; (2)School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou 510275, China
  • 收稿日期:2009-03-30 修回日期:2009-04-28 出版日期:2009-12-20 发布日期:2009-12-20
  • 基金资助:
    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

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)   

  1. 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
  • Received:2009-03-30 Revised:2009-04-28 Online:2009-12-20 Published:2009-12-20
  • Supported by:
    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

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摘要： 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-erbα-/- -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-erbα-/- mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell.

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.

Key words: mammals, circadian clock, cAMP, transcriptional feedback loop

中图分类号:  (Circadian rhythms)

  • 87.18.Yt
87.17.-d (Cell processes) 87.19.L- (Neuroscience) 87.19.X- (Diseases)