Resetting central and peripheral circadian oscillators in transgenic rats

Resetting central and peripheral circadian oscillators in transgenic rats
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DOI:
10.1126/science.288.5466.682
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发表时间:
2000-04-28
期刊:
影响因子:
56.9
通讯作者:
Tei, H
Tei, H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yamazaki, S;Numano, R;Tei, H

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在多细胞生物中,昼夜节律振荡器被组织成多组织系统,其功能就像生物钟一样,根据环境周期调节生物体的活动,并提供内部时间框架。为了研究哺乳动物昼夜节律系统的组织,我们构建了一个转基因大鼠系,其中荧光素酶在小鼠Per1启动子的控制下有节奏地表达。这些大鼠培养的视交叉上核(SCN)的光发射始终具有强烈的节律性,并在体外持续了32天。肝、肺和骨骼肌也表达昼夜节律,在体外培养2至7个周期后,昼夜节律减弱。为了响应环境光周期的提前和延迟,SCN发光的昼夜节律比运动行为的节律或外周组织的节律转移得更快。我们假设SCN中自我维持的昼夜节律起搏器在外围携带昼夜节律振荡器以维持自适应相位控制,该相位控制在环境光周期的大突变后暂时丢失。
In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat Line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, Lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental Light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily Lost following Large, abrupt shifts in the environmental Light cycle.