A novel circadian behavior rhythm in arrhythmic triple knockout mice revealed by constant light exposure.

The current model for autonomous circadian oscillation is based on the transcriptional-translational feedback loops of circadian genes. The deletion of one of the circadian genes and its paralogs leads to arrhythmicity. triple knockout ( KO) mice exhibit arrhythmic behavior in constant darkness. Molecular oscillations in the primary pacemaker in the suprachiasmatic nucleus (SCN) and peripheral oscillators are blunted in these mice. Here we report that a simple environmental manipulation, constant light exposure (LL), revealed a ∼22 h behavior rhythm in KO mice. SCN explanted from behaviorally rhythmic KO mice showed disrupted calcium rhythms, suggesting that the rescued rhythm is likely independent of the SCN. Although the mechanism by which LL reveals residual circadian rhythm in KO mice remains to be discovered, this unexpected novel effect of LL is greatly contrary to the well-documented disruptive effect of LL on the SCN clock in wildtype rodents.