title: Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms.
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 clock is composed of an autoregulatory transcription-(post) translation-based feedback loop involving a set of 'dock' 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 Cryl 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 Cryl 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.
authors.affiliation: MGC, Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: G T
authors.initials: GT
authors.lastname: van der Horst
authors.forename: M
authors.initials: M
authors.lastname: Muijtjens
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: R
authors.initials: R
authors.lastname: Takano
authors.forename: S
authors.initials: S
authors.lastname: Kanno
authors.forename: M
authors.initials: M
authors.lastname: Takao
authors.forename: J
authors.initials: J
authors.lastname: de Wit
authors.forename: A
authors.initials: A
authors.lastname: Verkerk
authors.forename: A P
authors.initials: AP
authors.lastname: Eker
authors.forename: D
authors.initials: D
authors.lastname: van Leenen
authors.forename: R
authors.initials: R
authors.lastname: Buijs
authors.forename: D
authors.initials: D
authors.lastname: Bootsma
authors.forename: J H
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: A
authors.initials: A
authors.lastname: Yasui
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005260:Female; D005420:Flavoproteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D016296:Mutagenesis; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D043562:Receptors, G-Protein-Coupled; C119828:cry protein, Drosophila