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

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 <i>Bmal1</i> promoter-driven luciferase (<i>Bmal1-Luc</i>) reporter gene. Next, dexamethasone was applied for various cyclic stimulations, which revealed that <i>Bmal1</i> 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 <i>Npas2</i> 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.