A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1
A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1
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DOI：
10.1046/j.1365-2443.1999.00238.x
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发表时间：
1999-01-01
期刊：
影响因子：
2.1
通讯作者：
Okamura, H
中科院分区：
文献类型：
--
作者：
Takumi, T;Nagamine, Y;Okamura, H
背景：现在越来越清楚的是，行为和激素的昼夜节律源于基因表达水平的节律，并且哺乳动物和果蝇本质上使用同源基因作为控制昼夜节律振荡的分子齿轮。在果蝇中，周期基因和永恒基因形成了时钟的功能单元及其昼夜节律的自动调节反馈回路。然而，在哺乳动物中，尚未发现timeless的对应物。结果：我们从小鼠大脑中分离出了timeclass的哺乳动物同源物mTim。 mTim 在哺乳动物昼夜节律中心视交叉上核中高度表达，节律较弱或不存在。在视网膜中，发现 mTim mRNA 以昼夜节律表达，并且在存在光/暗周期的情况下观察到特别强劲的周期。我们证明了 mTIM 在体外和培养的 COS7 细胞核中与 mPER1 物理结合。结论：我们报道了小鼠 timeless cDNA 的分离、mTim mRNA 的表达以及 mTIM 与 mPER1 的相互作用。这些结果表明 period 基因昼夜节律振荡的自动调节反馈机制在哺乳动物中也可能是保守的。
Background: It is now becoming clear that the circadian rhythm of behaviours and hormones arises from a rhythm at the level of gene expression, and that mammals and Drosophila essentially use homologous genes as molecular gears in the control of circadian oscillation. In Drosophila, the period and timeless genes form a functional unit of the clock and its autoregulatory feedback loop for circadian rhythm. However, in mammals, the counterpart of timeless has not been found.Results: We have isolated a mammalian homologue of timeclass, mTim, from the mouse brain. mTim is highly expressed, with a weak or absent rhythm in the suprachiasmatic nucleus, the mammalian circadian centre, In the retina, mTim mRNA was found to be expressed with a circadian rhythm, and a particularly robust cycle was observed in the presence of light/dark cycles. We demonstrated that mTIM physically associates with mPER1 in vitro and in the nuclei of cultured COS7 cells.Conclusions: We have reported the isolation of the mouse timeless cDNA, the expression of the mTim mRNA and an interaction of mTIM with mPER1, These results indicate that the autoregulatory feedback mechanism of circadian oscillation of the period gene may also be conserved in mammals.