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.
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In all nucleated cells, four families of core clock genes (Clock, Bmal1, Period, and Cryptochrome) form a transcription-translation feedback loop that cycles every approximately 24 hours.
“In all nucleated cells, four families of core clock genes (Clock, Bmal1, Period [Per], and Cryptochrome [Cry]) form a transcriptiontranslation feedback loop that cycles every approximately 24 hours (reviewed in refs.[28][29][30][31][32][33][34][35].”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [29]
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- Authors
- Horst, G. T. J. V. D., Muijtjens, M., Kobayashi, K., Takano, R., Kanno, S.-I., Takao, M., Wit, J. D., Verkerk, A., Eker, A. P. M., Leenen, D. V., Buijs, R., Bootsma, D., Hoeijmakers, J. H. J., & Yasui, A.
- Affiliations
- Erasmus University Rotterdam (NL)
- Tohoku University (JP)
- ORCID
- Venue
- Nature
- Published
- 1999-04
- Volume
- 398
- Issue
- 6728
- Pages
- 627-630
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1744822607
- Cited by
- 1,402
- References
- 29
- Citations by year
- 2026: 22 · 2025: 40 · 2024: 40 · 2023: 44 · 2022: 68 · 2021: 66 · 2020: 55 · 2019: 48 · 2018: 64 · 2017: 46 · 2016: 55 · 2015: 55 · 2014: 57 · 2013: 60 · 2012: 44
- FWCI
- 28.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Frequency and Time Standards
- Keywords
- cryptochrome, CRY1, CRY2, circadian rhythm, biological clock, locomotor activity, free-running period, photoreception, light entrainment, clock genes, knockout mice, photolyase
- MeSH terms
- Animals, Biological Clocks, Cell Line, Circadian Rhythm, Eye Proteins, Female, Flavoproteins, Male, Mice, Inbred C57BL, Motor Activity, Mutagenesis, Photoreceptor Cells, Invertebrate, Mice, Knockout, Drosophila Proteins, Receptors, G-Protein-Coupled, Mice, Cryptochromes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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