The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease.
The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease.
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DOI：
10.1073/pnas.2121883119
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发表时间：
2022-08-09
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
昼夜节律振荡器的相位错位发生在日程安排的改变时。这些影响（例如时差反应）会对健康产生不利影响。我们对决定昼夜节律振荡器恢复最佳相位关系的速度的因素缺乏了解。我们发现，在光：暗周期转移后，隐花色素 1 (Cry1) 缺失的 duper 突变仓鼠和 Cry1−/− 小鼠中的重新夹带都会加速。杜珀突变加速生物钟的作用对于其重新夹带的加速并不重要。 Duper 会缩短心肌病动物的寿命，但重复的相移会阻止这种效应。 Duper 可以阐明决定时差和轮班工作有害影响程度的途径。隐花色素 1 (Cry1) 缺陷的 duper 突变仓鼠在恒定黑暗 (τDD) 中具有较短的自由奔跑期，并且对短暂的光脉冲表现出较大的相移。我们测试了这种昼夜节律不稳定性的测量是否是 Cry1 缺失动物的一般特征，以及它是否表明对时差反应的抵抗力。在光：暗（LD）周期推进后，欺骗仓鼠和 Cry1−/− 小鼠重新控制运动节律的速度是野生型的三倍。然而，加速再夹带与放大的相位响应曲线（PRC）无关：与傻仓鼠不同，Cry1−/− 小鼠对 15' 光脉冲的相位响应没有放大。突变体中急剧变化的放大和重新夹带率的增加都不是由于生物钟的加速：当突变体喝重水以延长周期时，表型的这些方面仍然存在。鉴于昼夜节律失调对健康的影响，我们研究了重复和相移对仓鼠心脏病模型的影响，此前研究表明重复相移会加剧心脏病。与野生型相比，这种突变缩短了心肌病仓鼠的寿命，但当突变体每两周经历 8 小时的相移并迅速重新进入相移时，这种效应就被消除了。我们的结果揭示了 Cry1 在面对心脏病时的相移和长寿方面的先前未曾怀疑的作用。欺骗突变体为了解昼夜节律紊乱和时差反应的基础提供了新的机会。
Misalignment of the phase of circadian oscillators occurs upon shifts of schedule. The effects, such as occur in jet lag, have adverse effects on health. We lack understanding of factors that determine how rapidly optimal phase relationships of circadian oscillators are regained. We find that re-entrainment is accelerated in both duper mutant hamsters, which are Cryptochrome 1 (Cry1) null, and Cry1−/− mice after the light:dark cycle is shifted. The effect of the duper mutation to speed the circadian clock is not essential to its acceleration of re-entrainment. Duper shortens the lifespan of cardiomyopathic animals, but repeated phase shifts block this effect. Duper can elucidate pathways that determine the extent of deleterious effects of jet lag and shift work. The Cryptochrome 1 (Cry1)–deficient duper mutant hamster has a short free-running period in constant darkness (τDD) and shows large phase shifts in response to brief light pulses. We tested whether this measure of the lability of the circadian phase is a general characteristic of Cry1-null animals and whether it indicates resistance to jet lag. Upon advance of the light:dark (LD) cycle, both duper hamsters and Cry1−/− mice re-entrained locomotor rhythms three times as fast as wild types. However, accelerated re-entrainment was dissociated from the amplified phase-response curve (PRC): unlike duper hamsters, Cry1−/− mice show no amplification of the phase response to 15’ light pulses. Neither the amplified acute shifts nor the increased rate of re-entrainment in duper mutants is due to acceleration of the circadian clock: when mutants drank heavy water to lengthen the period, these aspects of the phenotype persisted. In light of the health consequences of circadian misalignment, we examined effects of duper and phase shifts on a hamster model of heart disease previously shown to be aggravated by repeated phase shifts. The mutation shortened the lifespan of cardiomyopathic hamsters relative to wild types, but this effect was eliminated when mutants experienced 8-h phase shifts every second week, to which they rapidly re-entrained. Our results reveal previously unsuspected roles of Cry1 in phase shifting and longevity in the face of heart disease. The duper mutant offers new opportunities to understand the basis of circadian disruption and jet lag.
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影响因子：
3.7
作者：
Bittman EL
通讯作者：
Bittman EL
影响因子：
3.3
作者：
GROSSE, J;LOUDON, ASI;HASTINGS, MH
通讯作者：
HASTINGS, MH
DOI：
10.1111/febs.15360
发表时间：
2021-01
期刊：
The FEBS journal
影响因子：
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作者：
Cal-Kayitmazbatir S;Kulkoyluoglu-Cotul E;Growe J;Selby CP;Rhoades SD;Malik D;Oner H;Asimgil H;Francey LJ;Sancar A;Kruger WD;Hogenesch JB;Weljie A;Anafi RC;Kavakli IH
通讯作者：
Kavakli IH
影响因子：
3.5
作者：
Beersma, Domien G. M.;van Bunnik, Bram A. D.;Daan, Serge
通讯作者：
Daan, Serge
影响因子：
9.9
作者：
通讯作者：
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