Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms

• Published in: Nature (London) Vol. 398; no. 6728; pp. 627 - 630
• Main Authors: Hoeijmakers, Jan H. J, Horst, Gijsbertus T. J. van der, Muijtjens, Manja, Kobayashi, Kumiko, Takano, Riya, Kanno, Shin-ichiro, Takao, Masashi, Wit, Jan de, Verkerk, Anton, Eker, Andre P. M, Leenen, Dik van, Buijs, Ruud, Bootsma, Dirk, Yasui, Akira
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 15.04.1999; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Biological clocks; Biological Clocks - genetics; Biological Clocks - physiology; Cell Line; Circadian rhythm; Circadian Rhythm - genetics; Circadian Rhythm - physiology; Classical genetics, quantitative genetics, hybrids; Cryptochromes; Drosophila Proteins; Eye Proteins; Female; Flavoproteins - genetics; Flavoproteins - physiology; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Male; Mammals; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; Mutagenesis; Photoreceptor Cells, Invertebrate; Proteins; Receptors, G-Protein-Coupled; Vertebrata; Vertebrata; Mammalia; Targeting; Gene; Mouse; Rodentia; Biological rhythm; Mutation; Circadian rhythm
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/19323

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' genes,. 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 clock. 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.