A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.

A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.
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人的睡眠体内平衡表型在表达灵长类动物特异性PER3的可变串联编码区域多态性的小鼠中。

DOI:
10.1096/fj.13-240135
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发表时间:
2014-06
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
通讯作者:
Archer SN
Archer SN
中科院分区:
其他
文献类型:
--
作者:
Hasan S;van der Veen DR;Winsky-Sommerer R;Hogben A;Laing EE;Koentgen F;Dijk DJ;Archer SN

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在人类中,昼夜节律基因PER3中的灵长类特异性可变数串联重复(VNTR)多态性(4或5个重复长度为54 nt)与睡眠时间的差异和睡眠缺失的稳态反应有关。我们研究了这种多态性对昼夜节律和睡眠稳态的影响,将多态性引入小鼠,并在基线、睡眠剥夺(SD)期间和12小时后评估昼夜节律和睡眠参数。微阵列分析用于测量下丘脑和皮层的基因表达。生理行为和睡眠在基线时正常。Per35/5小鼠清醒时脑电图θ功率和睡眠时脑电图δ功率对SD的响应更大。在恢复过程中,Per35/5小鼠完全补偿了sd诱导的δ功率缺陷,而Per34/4和野生型小鼠则没有。睡眠稳态相关转录物(如Homer1、Ptgs2和Kcna2)在人源化小鼠之间的表达存在差异,但生物钟基因没有差异。这些数据与基于人类数据的假设一致,即PER3 VNTR多态性可以改变睡眠稳态反应,而不会显著影响昼夜节律参数。-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E., Koentgen, F., Dijk, D.- j。表达灵长类特异性PER3可变数串联重复编码区多态性的小鼠的人类睡眠稳态表型。
In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) θ power during wakefulness and δ power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in δ power, but the Per34/4 and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.—Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.
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