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光导引异常导致Chrono敲除小鼠代谢紊乱

王若晗^1,2, 蓝韶颖^1,2, 曹博远^1,2, 秦曦明^1,2,*

¹安徽大学物质科学与信息技术研究院，合肥 230601；²安徽大学健康科学与技术研究所，合肥 230601

摘要

地球上的多数生命在长期受周期性昼夜环境变化的影响下，逐渐进化出内源性生物钟系统，这一系统对生命活动的有序进行意义重大。在哺乳动物，下丘脑视交叉上核是昼夜节律的调控中枢。生物钟的运行依赖于转录-翻译负反馈环路，CHRONO作为该环路的负调控因子，研究尚不完全。为深入探究Chrono基因在节律导引中的作用及生理功能，本研究通过CRISPR/Cas9技术构建了Chrono基因敲除小鼠模型，系统研究了其在不同T循环下的导引特征，并通过小鼠跑轮实验、葡萄糖耐量实验对其生理功能进行分析。实验结果表明，Chrono敲除小鼠的内源生物钟周期延长，T21 循环下的导引率降低。此外，未导引的Chrono敲除小鼠出现体重增加、葡萄糖耐量受损等代谢紊乱。上述研究揭示了Chrono基因在维持昼夜节律和代谢稳态中的重要作用，为理解生物钟与代谢调控的关联提供了新视角。未来研究需要进一步解析其分子机制及其他潜在因素。

关键词： 生物钟; Chrono; 葡萄糖耐量实验; 代谢综合征; CRISPR-Cas系统

Misaligned light entrainment causes metabolic disorders in Chrono knockout mice

WANG Ruo-Han^1,2, LAN Shao-Ying^1,2, CAO Bo-Yuan^1,2, QIN Xi-Ming^1,2,*

¹Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China；²Institute of Health Sciences and Technology, Anhui University, Hefei 230601, China

Abstract

Most of the life forms on Earth have gradually evolved an endogenous biological clock under the long-term influence of periodic daily light-dark cycles. This biological clock system plays a crucial role in the orderly progression of life activities. In mammals, central circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and the function of the biological clock relies on a transcription-translation negative feedback loop. As a negative regulator in this loop, the function of CHRONO is less known. To deeply explore the role of the Chrono gene in rhythm entrainment and physiology, we constructed a Chrono gene knockout mouse strain using the CRISPR/Cas9 technology and analyzed its entrainment ability under different T cycles. Running wheel tests and glucose tolerance tests were also performed. The results showed that the period of the endogenous biological clock of Chrono knockout mice was prolonged, and the entrainment rate under the T21 cycle was decreased. In addition, metabolic abnormalities, including weight gain and impaired glucose tolerance, were observed in the non-entrained mice. Overall, this study reveals a crucial role of the Chrono gene in maintaining circadian rhythms and metabolic balance, providing a new perspective for understanding the relationship between the biological clock and metabolism. Further research is needed to fully understand the underlying molecular mechanisms.

Key words: circadian clock; Chrono; glucose tolerance test; metabolic syndrome; CRISPR-Cas systems

收稿日期：　　录用日期：

通讯作者：秦曦明　　E-mail:

DOI: 10.13294/j.aps.2025.0061

引用本文：

王若晗, 蓝韶颖, 曹博远, 秦曦明. 光导引异常导致Chrono敲除小鼠代谢紊乱[J]. 生理学报 2025; 77 (4): 731-740.

WANG Ruo-Han, LAN Shao-Ying, CAO Bo-Yuan, QIN Xi-Ming. Misaligned light entrainment causes metabolic disorders in Chrono knockout mice. Acta Physiol Sin 2025; 77 (4): 731-740 (in Chinese with English abstract).