Molecular Mechanisms of the Biological Clock in Cultured Fibroblasts

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Science  13 Apr 2001:
Vol. 292, Issue 5515, pp. 278-281
DOI: 10.1126/science.1059542

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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 andcryptochrome (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 functionalmCry genes, and (v) the control of period length by mCRY proteins.

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