Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag,European Journal of Neuroscience

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Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2020-12-22 , DOI: 10.1111/ejn.15085
Yoichi Minami ₁ , Tomoko Yoshikawa ₁ , Mamoru Nagano ₁ , Satoshi Koinuma ₁ , Tadamitsu Morimoto ₁ , Atsuko Fujioka ₁ , Keiichi Furukawa ₁ , Keisuke Ikegami ₁ , Atsuhiro Tatemizo ₂ , Kentaro Egawa ₂ , Teruya Tamaru ₃ , Taizo Taniguchi ₄ , Yasufumi Shigeyoshi ₁

Affiliation

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.

中文翻译：

表达显性阴性 BMAL1 的转基因大鼠表现出生物钟振幅降低和时差快速恢复

昼夜节律是大约 24 小时的内源性节律，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，但在环境照明条件突然变化后，视交叉上核的一部分会导致时差。为了检查减弱的昼夜节律对时差持续时间的影响，我们建立了一只表达 BMAL1 显性阴性形式的转基因大鼠，该大鼠受基于小鼠Prnp的转录调节盒 [BMAL1 DN (+)] 的控制。转基因大鼠比对照组更早地变得活跃，就在光照偏移之后。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。夜间的光脉冲导致行为节律的较大相移。此外，在明暗周期的突然转变中，与对照组相比，BMAL1 DN (+) 大鼠对新的明暗周期的夹带速度更快。昼夜节律被认为是一种极限循环现象，我们的结果支持这样的假设，即改变昼夜节律极限循环的幅度会导致相移长度的改变。

更新日期：2020-12-22

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