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The mPer2 gene encodes a functional component of the mammalian circadian clock

Nature volume 400, pages 169–173 (1999)Cite this article

Abstract

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms1. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified2,3,4,5,6,7,8. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.

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Figure 1: Generation of mPer2 Brdm1 mutant mice.
Figure 2: Representative locomotor activity records of F2 wild-type and homozygous mPer2 Brdm1 mutant mice.
Figure 3: Fourier analysis of periodicity of F2 wild-type and homozygous mPer2 Brdm1 mutants.
Figure 4: Expression analysis of F2 wild-type and homozygous mPer2 Brdm1 mutant mice in LD 12:12.

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Acknowledgements

We thank S. Vaishnav, L. Qiu, Y.-C. Cheah, E. Sheppeard and S. Rivera for technical assistance; P. Hastings for comments on the manuscript; J. W. Patrick for providing space and facilities for circadian phenotype analysis; and J. Takahashi, Y. Zhao and M. Bucan for helpful discussions. This work was supported by grants from NINDS and NIDA to J. W. Patrick, from the Max-Planck Society to G. E., from NIH and the Department of Defense to C.C.L., and from NIH and the Howard Hughes Medical Institute to A.B. A.B. is an investigator with HHMI.

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Author notes

  1. Urs Albrecht & Gregor Eichele

    Present address: Max Planck Institute for Experimental Endocrinology, Feodor-Lynen-Strasse 7, 30625, Hanover, Germany

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Houston, 77030, Texas, USA

    Binhai Zheng, Zhong Sheng Sun, Marijke Sage, Cheng Chi Lee & Allan Bradley

  2. Division of Neuroscience, Houston, 77030, Texas, USA

    David W. Larkin

  3. Verna and Marrs McLean Department of Biochemistry, Houston, 77030, Texas, USA

    Urs Albrecht & Gregor Eichele

  4. Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Allan Bradley

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Correspondence to Cheng Chi Lee.

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Zheng, B., Larkin, D., Albrecht, U. et al. The mPer2 gene encodes a functional component of the mammalian circadian clock. Nature 400, 169–173 (1999). https://doi.org/10.1038/22118

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