Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis.
Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis.
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DOI：
10.1371/journal.pone.0008552
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发表时间：
2010-01-01
期刊：
影响因子：
3.7
通讯作者：
Yamazaki S
中科院分区：
文献类型：
--
作者：
Pendergast JS;Friday RC;Yamazaki S
哺乳动物昼夜节律系统由视交叉上核（SCN）中的主起搏器以及大脑和外周组织中的其他振荡器组成，控制行为和生理的日常节律。SCN的病变消除了运动活动的昼夜节律，并且胎儿SCN组织的移植恢复了具有供体基因型的周期性的节律行为，这表明SCN决定了昼夜行为节律的周期。根据SCN中的计时模型，Period（Per）基因是产生内源性昼夜节律的转录/翻译反馈回路的重要元件。先前的研究通过检查缺乏功能性PERIOD蛋白的小鼠的运动活动来研究Per基因的功能。根据小鼠的品系和遗传背景，观察到可变的行为表型。在目前的研究中，我们评估了与C57 BL/6 J品系同源的Per 2 −/−和Per 3 −/−小鼠培养的SCN、垂体和肺外植体中的轮跑活性和Per 1启动子驱动的荧光素酶表达（Per 1-luc）。我们发现，与体内相比，Per 2 −/−表型在体外增强，因此Per 2 −/− SCN外植体中Per 1-luc表达的时间比Per 2 +/+ SCN中短1.5小时，而Per 2 −/−小鼠中车轮活动的自由运行时间仅比Per 2 +/+小鼠短11分钟。相比之下，Per 3 −/−小鼠SCN外植体的昼夜节律与Per 3 +/+小鼠没有差异。相反，与Per 3 +/+小鼠相比，Per 3 −/−垂体和肺外植体中Per 1-luc表达的时期和阶段发生了显著改变。综合这些数据表明，每个Per基因的功能在组织之间可能不同。Per 2似乎是重要的SCN期间确定，而Per 3参与在垂体和肺计时。
The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN) as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per) genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc) in cultured SCN, pituitary, and lung explants from Per2−/− and Per3−/− mice congenic with the C57BL/6J strain. We found that the Per2−/− phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per2−/− SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per2−/− compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per3−/− mice do not differ from Per3+/+ mice. Instead, the period and phase of Per1-luc expression are significantly altered in Per3−/− pituitary and lung explants compared to Per3+/+ mice. Taken together these data suggest that the function of each Per gene may differ between tissues. Per2 appears to be important for period determination in the SCN, while Per3 participates in timekeeping in the pituitary and lung.
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