Adaptive Differences in Cellular and Behavioral Responses to Circadian Disruption between C57BL/6 and BALB/c Strains

C57BL/6 和 BALB/c 品系对昼夜节律紊乱的细胞和行为反应的适应性差异

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作者:Changxiao Ma, Haonan Li, Wenyu Li, Guangrui Yang, Lihong Chen

Abstract

The regulation of the mammalian circadian clock is largely dependent on heredity. In model animals for circadian rhythm studies, C57BL/6 and BALB/c mice exhibit considerable differences in their adaptation to circadian disruption, yet deeper comparisons remain unexplored. Here, we have established embryonic fibroblast cells derived from C57BL/6 mice (MEF) and BALB/c (BALB/3T3) mice, which have been transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Next, dexamethasone was applied for various cyclic stimulations, which revealed that Bmal1 bioluminescence of MEF cells was entrained to 24 to 26 h cycles, whereas BALB/3T3 cells have a wider range (22 to 28 h) with lower amplitudes. Behaviorally, BALB/c mice swiftly adapted to a 6-h advance light/dark cycle, unlike C57BL/6 mice. Furthermore, we found the expression of the circadian rhythm gene Npas2 in BALB/c mice is significantly lower than that in C57BL/6 mice. This observation is consistent with the differentially expressed genes (DEGs) in the intestine and lung tissues of C57BL/6 and BALB/c mice, based on the RNA-seq datasets downloaded from the Gene Expression Omnibus (GEO). In summary, our study uncovers that BALB/c mice possess greater resilience in circadian rhythm than C57BL/6 mice, both cellular and behaviorally, identifying potential genes underlying this difference.

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