the role of p53 gene in maintenance of circadian rhythm

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Previous studies have shown that the incidence of cardiovascular events is closely associated with circadian rhythm. It is recently reported that p53 is one of the important factors modulating the development of cardiovascular disease. However, it remains unknown whether p53 affects circadian rhythm. We examined the role of p53 gene in circadian rhythm by analyzing p53 knockout mice.Daily oscillations of behavior were analyzed with actogram. P53 knockout mice demonstrated insufficient response to the light pulse and couldn't catch up the clock-resetting. Mouse embryonic fibroblast isolated from p53 knockout mice also showed the defect of p53 attenuated the oscillations of Per2 gene. Besides, microarray analysis supported the requirement of p53 gene to keep circadian rhythm intact. From these results, it is suggested that p53 can affect circadian rhythm through some feedback pathway via Per genes and may lead to modulate the incidence of vascular events.