Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock

The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during ext ended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficie nt mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Beh avioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, con firming the placement of mPer3 outside the core circadian clockwork. In con trast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mP ER1 influences rhythmicity primarily through interaction with other clock p roteins, while mPER2 positively regulates rhythmic gene expression, and the re is partial compensation between products of these two genes.