Mouse genotypes drive the liver and adrenal gland clocks - whole exome sequencing of two mouse strains.

Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. We show that the genotype of mouse lines defines the circadian gene expression patterns. Expression of the majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in light – dark conditions (LD), exome sequencing and data mining all together proposed that mouse lines differ in perception of the light signal. This is supported by the genotype effect in adrenal glands that is largest under LD and by the high number of single nucleotide variants in the G protein coupled receptor melanopsin. Other subtle circadian differences can result from the changed amino acid sequence of the Period 2 protein and from single nucleotide variants in the core clock gene promoters.