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 and Akira Yasui
Additional contact information
Gijsbertus T. J. van der Horst: MGC, Erasmus University
Manja Muijtjens: MGC, Erasmus University
Kumiko Kobayashi: Institute of Development, Aging and Cancer, Tohoku University
Riya Takano: Institute of Development, Aging and Cancer, Tohoku University
Shin-ichiro Kanno: Institute of Development, Aging and Cancer, Tohoku University
Masashi Takao: Institute of Development, Aging and Cancer, Tohoku University
Jan de Wit: MGC, Erasmus University
Anton Verkerk: MGC, Erasmus University
Andre P. M. Eker: MGC, Erasmus University
Dik van Leenen: MGC, Erasmus University
Ruud Buijs: Netherlands Institute for Brain Research
Dirk Bootsma: MGC, Erasmus University
Jan H. J. Hoeijmakers: MGC, Erasmus University
Akira Yasui: Institute of Development, Aging and Cancer, Tohoku University

Nature, 1999, vol. 398, issue 6728, 627-630

Abstract: Abstract Many biochemical, physiological and behavioural processes show circadian rhythms which are generated by an internal time-keeping mechanism referred to as the biological clock. According to rapidly developing models, the core oscillator driving this clockis composed of an autoregulatory transcription–(post) translation-based feedback loop involving a set of ‘clock’ genes1,6. Molecular clocks 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 clock7,8,9,10. 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.

Date: 1999
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DOI: 10.1038/19323

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