Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag
Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag
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DOI：
10.1111/ejn.15085
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发表时间：
2020-12
影响因子：
3.4
通讯作者：
Y. Minami;T. Yoshikawa;M. Nagano;Satoshi Koinuma;Tadamitsu Morimoto;Atsuko Fujioka;Keiichi Furukawa;Keisuke Ikegami;Atsuhiro Tatemizo;Kentaro Egawa;T. Tamaru;T. Taniguchi;Y. Shigeyoshi
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文献类型：
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作者：
Y. Minami;T. Yoshikawa;M. Nagano;Satoshi Koinuma;Tadamitsu Morimoto;Atsuko Fujioka;Keiichi Furukawa;Keisuke Ikegami;Atsuhiro Tatemizo;Kentaro Egawa;T. Tamaru;T. Taniguchi;Y. Shigeyoshi
昼夜节律是24小时左右的内源性节律，由生物钟驱动。时钟中心位于视交叉上核。来自视网膜的光信号改变了视交叉上核的昼夜节律，但视交叉上核中有一个强大的部分在环境光照条件突然改变后引起时差反应。为了研究昼夜节律减弱对时差持续时间的影响，我们在小鼠基于Prnp的转录调节盒[BMAL1 DN(+)]的控制下，建立了表达BMAL1显性阴性形式的转基因大鼠。转基因大鼠比对照组更早变得活跃，就在光抵消之后。与对照大鼠相比，BMAL1 DN（+）大鼠在行为和Per2启动子驱动的荧光素酶活性节律中均表现出较小的昼夜节律幅度。夜间的光脉冲导致行为节律的较大相移。此外，在光-暗周期的突变中，BMAL1 DN（+）大鼠对新的光-暗周期的反应比对照组更快。昼夜节律一直被认为是一种极限环现象，我们的研究结果支持了昼夜节律极限环幅度的改变导致相移长度改变的假设。
The circadian rhythms are endogenous rhythms of about 24 h, and are driven by the circadian clock. The clock centre locates in the suprachiasmatic nucleus. Light signals from the retina shift the circadian rhythm in the suprachiasmatic nucleus, but there is a robust part of the suprachiasmatic nucleus that causes jet lag after an abrupt shift of the environmental lighting condition. To examine the effect of attenuated circadian rhythm on the duration of jet lag, we established a transgenic rat expressing BMAL1 dominant negative form under control by mouse Prnp‐based transcriptional regulation cassette [BMAL1 DN (+)]. The transgenic rats became active earlier than controls, just after light offset. Compared to control rats, BMAL1 DN (+) rats showed smaller circadian rhythm amplitudes in both behavioural and Per2 promoter driven luciferase activity rhythms. A light pulse during the night resulted in a larger phase shift of behavioural rhythm. Furthermore, at an abrupt shift of the light‐dark cycle, BMAL1 DN (+) rat showed faster entrainment to the new light‐dark cycle compared to controls. The circadian rhythm has been regarded as a limit cycle phenomenon, and our results support the hypothesis that modification of the amplitude of the circadian limit cycle leads to alteration in the length of the phase shift.