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The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN) as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the  Period (Per)  genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the  Per  genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and  Per1 -promoter-driven luciferase expression ( Per1-luc ) in cultured SCN, pituitary, and lung explants from  Per2 −/−   and  Per3 −/−   mice congenic with the C57BL/6J strain. We found that the  Per2 −/−   phenotype is enhanced  in vitro  compared to  in vivo , such that the period of  Per1-luc  expression in  Per2 −/−   SCN explants is 1.5 hours shorter than in  Per2 +/+   SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in  Per2 −/−   compared to  Per2 +/+   mice. In contrast, circadian rhythms in SCN explants from  Per3 −/−   mice do not differ from  Per3 +/+   mice. Instead, the period and phase of  Per1-luc  expression are significantly altered in  Per3 −/−   pituitary and lung explants compared to  Per3 +/+   mice. Taken together these data suggest that the function of each  Per  gene may differ between tissues.  Per2  appears to be important for period determination in the SCN, while  Per3  participates in timekeeping in the pituitary and lung.

Distinct Functions of Period2 and Period3 in the Mouse Circadian System Revealed by In Vitro Analysis