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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

Received: 　　Accepted:

Corresponding author: 秦曦明　　E-mail:

DOI: 10.13294/j.aps.2025.0061

Citing This Article：

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).