Molecular mechanisms of the biological clock in cultured fibroblasts
Molecular mechanisms of the biological clock in cultured fibroblasts
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DOI：
10.1126/science.1059542
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发表时间：
2001-04-13
期刊：
影响因子：
56.9
通讯作者：
Okamura, H
中科院分区：
文献类型：
--
作者：
Yagita, K;Tamanini, F;Okamura, H
在哺乳动物中，中央昼夜节律起搏器位于下丘脑视交叉上核(SCN)，但外周组织中也存在昼夜节律振荡器。在这里，利用来自mCry突变小鼠的野生型和隐色素(MCry)缺失的细胞系，我们证明了培养的成纤维细胞中的外周振荡器在以下方面与SCN中的振荡器相同：(I)所有已知时钟基因的时间表达谱，(Ii)各种mRNA节律的相位(即BMal1和mper基因的反相振荡)，(Iii)最高mRNA水平与核mPER1和mPER2蛋白出现之间的延迟，(Iv)在没有功能mCry基因的情况下不能产生振荡，以及(V)mCRY蛋白对周期长度的控制。
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.