title: Mouse genotypes drive the liver and adrenal gland clocks.
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.
authors.affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Košir
authors.affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.
authors.forename: Uršula
authors.initials: U
authors.lastname: Prosenc Zmrzljak
authors.affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.
authors.forename: Anja
authors.initials: A
authors.lastname: Korenčič
authors.affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Juvan
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.
authors.forename: Jure
authors.initials: J
authors.lastname: Ačimovič
authors.affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.|Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, Ljubljana, Slovenia.
authors.forename: Damjana
authors.initials: D
authors.lastname: Rozman
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D057225:Data Mining; D005838:Genotype; D008027:Light; D008099:Liver / Q000378:metabolism*; D008297:Male; D057507:Mice, 129 Strain / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics; D000073359:Exome Sequencing
chemical_list: D014157:Transcription Factors