Figure 1.

Canonical clock genes and the basic regulatory loop: impact on the kidney of genetic defects. In the most basic regulatory loop, Clock and Bmal1 are transcription factors that promote Cry and Per gene expression, and Cry and Per proteins, in turn, suppress Clock/Bmal1 induction of their Cry and Per transcription. Genetic disruption of some canonical clock genes has yielded renal-hypertension phenotypes as illustrated above for Clock, Bmal1, and Per1 in mice. Clock KO mice display loss of water and electrolyte excretion rhythmicity as well as differential responses to induction of kidney fibrosis, which appears specific of the driver of fibrosis (worse unilateral ureteral obstruction (UUO)-induced fibrosis but milder sodium overload-induced fibrosis). Bmal1 KO mice display accelerated aging, loss of rhythmicity of water excretion as well as non-dipping hypotension (red line) as compared to the normal blood pressure circadian rhythm (green line). Per1 KO mice display non-dipping hypertension (red line) as compared to the normal blood pressure circadian rhythm (green line).