Robust Circadian Rhythmicity of Per1 and Per2 Mutant Mice in Constant Light, and Dynamics of Per1 and Per2 Gene Expression under Long and Short Photoperiods

Abstract

The Per1 and Per2 genes are components of the mammalian circadian clock. Mutations in these genes alter phase resetting in response to a nocturnal light pulse, and Per2 mutant mice are known to become arrhythmic in constant darkness. We show that under constant light conditions, Per2 mutant mice exhibit robust activity rhythms as well as body temperature rhythms with a period length that is less than 24 h. In Per1 mutants, the period length of both activity and body temperature rhythms is longer than 24 h in constant light. Per1 mutants prolong their period length (tao) when illuminance is increased, whereas Per2 mutants shorten their endogenous period. Additionally, the authors show that the circadian pattern of Per1 and Per2 gene expression in mice is modified under different photoperiods and that there is a mutual influence of these genes on their timing of expression. We propose that, in mice, the phase relationship between Per1 and Per2 gene expression might be critical for transducing day length information to the organism. Per1 could be part of a morning oscillator tracking dawn, and Per2 could be part of an evening oscillator tracking dusk.

Effects of constant light on circadian rhythmicity in mice lacking functional cry genes: dissimilar from per mutants

“…The shortened in mPer2 Brdm1 mice in LL in two studies is a remarkable conWrmation of the deviant phenotype predicted by the molecular two-component model (Daan et al 2001). In our study there appeared to be no further shortening of the circadian cycle with increasing intensity beyond 1 lx in the mPer2 Brdm1 strain as was observed by Steinlechner et al (2002). An even shorter circadian period of circa 20 h in LL of circa 400 lx has been observed in mPer2 Brdm1 mCry1 ¡/¡ mice (Abraham et al 2006).…”

“…by Steinlechner et al (2002). Since we observed the light dependency in both directions this cannot be attributed to a sequence eVect.…”

“…According to the hypothesis by Daan et al (2001) the properties of the circadian system of mice with a deWcit in one of these genes should correspond with the properties of a circadian system with a deWcit in the E or M component. The results obtained by Steinlechner et al (2002) have conWrmed these predictions for mPer1 Brdm1 and mPer2 Brdm1 in constant light; the mCry1 and mCry2 mutant circadian properties in LL have not yet been studied. Here we test the predictions for both mCry1 and mCry2 knockout mice: mCry1 ¡/¡ mice were predicted to lengthen with increasing light intensity as found in mPer1 Brdm1 , while mCry2 ¡/¡ mice were predicted to shorten as observed in mPer2 Brdm1 .…”

“…Yet, the responses may be of considerable interest. So far, three studies have reported exceptional LL phenotypes in animals with mutant circadian genes: recovery from--rather than induction of--arrhythmicity in LL in mClock mutant mice (Spoelstra et al 2002) and mPer2/mCry1 double mutant mice (Abraham et al 2006), and shortening rather than lengthening of in LL in mPer2 mutant mice (Steinlechner et al 2002). These results suggest that it may be worthwhile to collect more information on rhythmicity in LL in circadian gene mutants.…”

“…Here we test the predictions for both mCry1 and mCry2 knockout mice: mCry1 ¡/¡ mice were predicted to lengthen with increasing light intensity as found in mPer1 Brdm1 , while mCry2 ¡/¡ mice were predicted to shorten as observed in mPer2 Brdm1 . We also repeat the study by Steinlechner et al (2002) to be able to compare the Cry and Per eVects quantitatively in the same study design, with both increasing and decreasing LL intensity.…”