Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms

Many biochemical, physiological and behavioural processes show circadian rh ythms which are generated by an internal timekeeping mechanism referred to as the biological clock. According to rapidly developing. models, the core oscillator driving this clock is composed of an autoregulatory transcriptio n-(post) translation-based feedback loop involving a set of 'clock' genes(1 -6). Molecular docks do not oscillate with an exact 24-hour rhythmicity but are entrained to solar day/night rhythms by light. The mammalian proteins Cry1 and Cry2, which are members of the family of plant blue-light receptor s (cryptochromes) and photolyases, have been proposed as candidate light re ceptors for photoentrainment of the biological clock(7-10). Here we show th at mice lacking the Cry1 or Cry2 protein display accelerated and delayed fr ee-running periodicity of locomotor activity, respectively. Strikingly, in the absence of both proteins, an instantaneous and complete loss of free-ru nning rhythmicity is observed. This suggests that, in addition to a possibl e photoreceptor and antagonistic clock-adjusting function, both proteins ar e essential for the maintenance of circadian rhythmicity.