Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation
Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation
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DOI：
10.1093/sleep/28.4.395
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发表时间：
2005-04-01
期刊：
影响因子：
5.6
通讯作者：
Turek, F
中科院分区：
文献类型：
--
作者：
Laposky, A;Easton, A;Turek, F
研究目的：在小鼠和果蝇中，核心生物钟基因的缺失或突变会导致睡眠量、睡眠结构和对睡眠剥夺的恢复反应发生意想不到的变化，这一发现使人们对昼夜节律系统的功能有了新的认识，这些功能超出了其作为睡眠-觉醒周期定时调节器的作用。哺乳动物昼夜节律基因的转录/翻译反馈环中的关键转录因子是BMAL 1/Mop 3，其是CLOCK的异二聚体伴侣。先前表明，BMAL 1/Mop 3基因缺陷的小鼠在恒定黑暗中立即变得痴呆，并且在夹带和恒定条件下具有降低的运动活性水平。在这项研究中，我们测试了哺乳动物BMAL 1/Mop 3基因对睡眠-觉醒模式具有调节作用的假设。设计：在BMAL 1/Mop 3基因靶向缺失的小鼠中，记录了在夹带和自由奔跑条件下以及急性（6小时）睡眠剥夺后的EEG/EMG睡眠-觉醒模式。BMAL 1/Mop 3缺失的纯合子小鼠在24小时内显示出减弱的睡眠和觉醒分布节律。此外，这些小鼠表现出增加总睡眠时间，睡眠片段和EEG三角洲功率在基线条件下，和衰减的补偿反应急性sleep deprivation.Conclusions：这些新的数据加强了假设，昼夜节律系统的分子组成部分发挥了核心作用，在产生的睡眠和觉醒超越只是这些行为的警觉状态的时间。
Study objectives: The finding that deletion or mutation of core circadian clock genes in both mice and flies induce unexpected alterations in sleep amount, sleep architecture and the recovery response,to sleep deprivation, has led to new insights into functions of the circadian system that extend beyond its role as a regulator of the timing of the sleep-wake cycle. A key transcription factor in the transcriptional/translational feedback loop of mammalian circadian genes is BMAL1/Mop3, a heterodimeric partner to CLOCK. It was previously shown that mice deficient in the BMAL1/Mop3 gene become immediately arrhythmic in constant darkness and have reduced locomotor activity levels under entrained and constant conditions. In this study, we tested the hypothesis that the mammalian BMAL1/Mop3 gene would have regulatory effects on sleep-wake patterns.Design: In mice with targeted deletion of the BMAL1/Mop3 gene, EEG/EMG sleep-wake patterns were recorded under entrained and free-running conditions as well as following acute (6-hrs) sleep deprivation.Measurements and results: Mice homozygous for the BMAL1/Mop3 deletion showed an attenuated rhythm of sleep and wakefulness distribution across the 24-hr period. In addition, these mice showed increases in total sleep time, sleep fragmentation and EEG delta power under baseline conditions, and an attenuated compensatory response to acute sleep deprivation.Conclusions: These new data strengthen the hypothesis that molecular components of the circadian system play a central role in the generation of sleep and wakefulness beyond just the timing of these behavioral vigilance states.