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Valérie Mongrain^1,2,, Xuan Ruan^1,3,, Hugues Dardente^1,2,a, Erin E. Fortier^1,3 and Nicolas Cermakian^1,2,3,*

¹ Laboratory of Molecular Chronobiology, Douglas Mental Health University Institute, Montréal, QC, Canada, H4H 1R3
² Department of Psychiatry, and
³ Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada, H3A 2T5

Accumulating evidence indicate that molecular mechanisms generating circadian rhythms display some degree of tissue-specificity. More specifically, distinct patterns of expression for nuclear receptors of the ROR family indicate that the transcriptional control of the clock gene Bmal1 differs among tissues. This study aims to investigate the expression of Ror isoforms (Ror and Rort) and characterize the molecular mechanisms underlying their tissue-specific expression. The expression of Ror isoforms was assessed in mouse liver, muscle, thymus and testis throughout 24 h using quantitative RT-PCR. Although the expression of Ror was rhythmic in the liver and thymus, it was constitutively expressed in muscle and testis. In contrast, the expression of Rort was constitutive in all four tissues. Furthermore, rhythmic expression of Ror was impaired in Clock mutant mice whereas the mutation had no effect on Rort expression. In line with these findings, luciferase assays revealed that transcription of the Ror promoter is clock-controlled whereas that of Rort promoter is essentially clock-independent. Our results provide insights into the molecular mechanisms that lead to differential expression of Ror and Rort and are suggestive of a framework that might account for tissue-specific circadian regulation.

These authors contributed equally to this work.

^aPresent address: School of Biological Sciences, University of Aberdeen, Aberdeen, Scotland, UK.

^* Correspondence: nicolas.cermakian{at}mcgill.ca