Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M, Block G D, Sakaki Y, Menaker M, Tei H
NSF Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22903-2477, USA.
Science. 2000 Apr 28;288(5466):682-5. doi: 10.1126/science.288.5466.682.
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.
在多细胞生物中，昼夜节律振荡器被组织成多组织系统，这些系统作为生物钟发挥作用，调节生物体相对于环境周期的活动，并提供一个内部时间框架。为了研究哺乳动物昼夜节律系统的组织方式，我们构建了一种转基因大鼠品系，其中荧光素酶在小鼠Per1启动子的控制下有节律地表达。这些大鼠培养的视交叉上核（SCN）发出的光始终呈现强烈的节律性，并且在体外持续长达32天。肝脏、肺和骨骼肌也表现出昼夜节律，在体外经过两到七个周期后节律消失。响应环境光周期的提前和延迟，SCN发出的光的昼夜节律比运动行为的节律或外周组织的节律变化更快。我们假设，SCN中一个自我维持的昼夜节律起搏器带动外周的昼夜节律振荡器，以维持适应性相位控制，而在环境光周期发生大的突然变化后，这种控制会暂时丧失。
