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Science 292 (5515): 278-281

Copyright © 2001 by the American Association for the Advancement of Science

Molecular Mechanisms of the Biological Clock in Cultured Fibroblasts

Kazuhiro Yagita,1 Filippo Tamanini,2 Gijsbertus T. J. van der Horst,2 Hitoshi Okamura1*

In mammals, the central circadian pacemaker resides in the hypothalamic suprachiasmatic nucleus (SCN), but circadian oscillators also exist in peripheral tissues. Here, using wild-type and cryptochrome (mCry)-deficient cell lines derived from mCry mutant mice, we show that the peripheral oscillator in cultured fibroblasts is identical to the oscillator in the SCN in (i) temporal expression profiles of all known clock genes, (ii) the phase of the various mRNA rhythms (i.e., antiphase oscillation of Bmal1 and mPer genes), (iii) the delay between maximum mRNA levels and appearance of nuclear mPER1 and mPER2 protein, (iv) the inability to produce oscillations in the absence of functional mCry genes, and (v) the control of period length by mCRY proteins.

1 Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
2 Center for Biomedical Genetics, Department of Cell Biology and Genetics, Erasmus University, Post Office Box 1738, 3000 DR, Rotterdam, Netherlands.
*   To whom correspondence should be addressed. E-mail: okamurah{at}

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