BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders.
BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders.
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BMAL1 基因敲除猕猴表现出睡眠减少和精神疾病
DOI：
10.1093/nsr/nwz002
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发表时间：
2019-01
影响因子：
20.6
通讯作者：
Chang HC
中科院分区：
文献类型：
--
作者：
Qiu P;Jiang J;Liu Z;Cai Y;Huang T;Wang Y;Liu Q;Nie Y;Liu F;Cheng J;Li Q;Tang YC;Poo MM;Sun Q;Chang HC
昼夜节律紊乱是代谢、精神和年龄相关疾病的危险因素，非人灵长类动物模型有助于开发治疗方法。在这里，我们报告了通过CRISPR/Cas9编辑猴胚胎来产生BMAL 1敲除食蟹猴的昼夜节律相关疾病。这些猴子表现出更高的夜间运动和睡眠减少，这进一步加剧了恒定的光照方案。生理昼夜节律的破坏反映了显着的抑制和代谢性血液激素水平。此外，BMAL 1缺陷的猴子表现出焦虑和抑郁，这与它们稳定升高的血液皮质醇以及在精神分裂症患者中发现的听觉oddball测试中的感觉处理缺陷一致。消融BMAL 1上调转录程序对炎症和应激反应，转录网络与人类睡眠剥夺，严重抑郁症和衰老。因此，BMAL 1基因敲除的猴子对于研究昼夜节律紊乱的生理后果以及开发昼夜节律和精神疾病的治疗方法是潜在有用的。
Abstract Circadian disruption is a risk factor for metabolic, psychiatric and age-related disorders, and non-human primate models could help to develop therapeutic treatments. Here, we report the generation of BMAL1 knockout cynomolgus monkeys for circadian-related disorders by CRISPR/Cas9 editing of monkey embryos. These monkeys showed higher nocturnal locomotion and reduced sleep, which was further exacerbated by a constant light regimen. Physiological circadian disruption was reflected by the markedly dampened and arrhythmic blood hormonal levels. Furthermore, BMAL1-deficient monkeys exhibited anxiety and depression, consistent with their stably elevated blood cortisol, and defective sensory processing in auditory oddball tests found in schizophrenia patients. Ablation of BMAL1 up-regulated transcriptional programs toward inflammatory and stress responses, with transcription networks associated with human sleep deprivation, major depressive disorders, and aging. Thus, BMAL1 knockout monkeys are potentially useful for studying the physiological consequences of circadian disturbance, and for developing therapies for circadian and psychiatric disorders.
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影响因子：
64.5
作者：
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DOI：
10.1126/science.1195027
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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