Abstract
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 majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in the adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in dark – dark (DD) and light – dark conditions (LD), exome sequencing and data mining proposed that mouse lines differ in single nucleotide variants in the binding regions of clock related transcription factors in open chromatin regions. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs. 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 Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. Different phenotypes of the two mouse lines and changed amino acid sequence of the Period 2 protein possibly contribute further to the observed differences in circadian gene expression.
Highlights
Circadian rhythms regulate a plethora of physiological processes
Mouse knock-out models of core clock genes were frequently derived by gene targeting of embryonic stem cells of 129 mouse strains[16,17,18] and the initial analyses performed on mice with a mixed genetic background, where results can be confounded by background effects[19]
We evaluated gene expression patterns of 10 core clock and 15 metabolic genes collected under dark – dark (DD) and light – dark conditions (LD) conditions (Supplementary Figs S1 and S2)
Summary
Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs 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 Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. The majority of organisms on Earth have evolved a robust inner body circadian (circa =approximately, dian =day) clock that ticks away in most of their cells. It controls physiological, behavioural and cellular processes, ranging from body temperature, sleep/wake and feeding rhythms to metabolism and hormone secretion[1]. Whole exome sequencing and in silico analyses were applied to expose the nucleotide variants which could contribute importantly to the observed differences in the circadian or diurnal patterns of genes expression (Fig. 1)
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