Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms

Gijsbertus T.J. Van Der Horst, Manja Muijtjens, Kumiko Kobayashi, Riya Takano, Shin Ichiro Kanno, Masashi Takao, Jan De Wit, Anton Verkerk, Andre P.M. Eker, Dik Van Leenen, Ruud Buijs, Dirk Bootsma, Jan H.J. Hoeijmakers, Akira Yasui

Research output: Contribution to journalArticlepeer-review

1124 Citations (Scopus)


Many biochemical, physiological and behavioural processes show circadian rhythms 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 transcription- (post) translation-based feedback loop involving a set of 'clock' genes1- 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 receptors (cryptochromes) and photolyases, have been proposed as candidate light receptors for photoentrainment of the biological clock7-10. Here we show that mice lacking the Cry1 or Cry2 protein display accelerated and delayed free-running periodicity of locomotor activity, respectively. Strikingly, in the absence of both proteins, an instantaneous and complete loss of free- running rhythmicity is observed. This suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity.

Original languageEnglish
Pages (from-to)627-630
Number of pages4
Issue number6728
Publication statusPublished - 1999 Apr 15

ASJC Scopus subject areas

  • General


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