Light-Dependent Behavioral Phenotypes in PER3-Deficient Mice

Abstract

A functional knockout of Period3 in mice (mPer3^{— / —} ) results in a mildly altered circadian phenotype, and mPer3 shows a redundant role within the circadian clock. In this study, the authors reevaluated the Per3^{—/ —} behavioral phenotype on a C57Bl/6J background and report altered responses to light. In constant light, free-running activity period was shorter than that of wild-type, whereas in constant darkness, no difference was observed between genotypes. The effect of light was parametric, and the difference in free-running period between genotypes increased under constant light with increasing light intensity. An attenuated response to light in Per3^{— / —} mice was also demonstrated through reduced negative masking in activity in an ultradian protocol and a slower reentrainment to a shifted light-dark cycle when activity falls in the light period of the new light-dark cycle. Behavioral phase-shifts in response to a single delaying or advancing light pulse in the Per3^—/— mouse were not compromised. This demonstrates that the mPer3^{— /—} phenotype is characterized predominantly by altered sensitivity to light and not by the ability of the circadian system to respond to light. In addition to its redundant role within the molecular clock, these data suggest a new role for Per3 outside of the circadian clock and contributing to light input pathways.