Cited by 718Circadian rhythm and melatoninSleep and Work-Related FatigueSleep and Wakefulness Research

The mPer2 gene encodes a functional component of the mammalian circadian clock

Zheng, Binhai, Larkin, David W., Albrecht, Urs, Sun, Zhong Sheng, Sage, Marijke, Eichele, Gregor, Lee, Cheng Chi, Bradley, Allan·1999·Nature

Abstract

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.

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Crossref · 10.1038/22118

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Authors
Zheng, B., Larkin, D. W., Albrecht, U., Sun, Z. S., Sage, M., Eichele, G., Lee, C. C., & Bradley, A.
Affiliations
  • Baylor College of Medicine (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Lee, Cheng Chi
Venue
Nature
Published
1999-07
Volume
400
Issue
6740
Pages
169-173
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1629086938
Cited by
718
References
29
Citations by year
2026: 16 · 2025: 21 · 2024: 22 · 2023: 19 · 2022: 28 · 2021: 28 · 2020: 25 · 2019: 17 · 2018: 28 · 2017: 31 · 2016: 24 · 2015: 20 · 2014: 32 · 2013: 35 · 2012: 20
FWCI
14.39
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
mPer2, circadian clock, period gene, PAS domain, suprachiasmatic nucleus, circadian period, circadian rhythmicity, mPer1, clock gene regulation, constant darkness
MeSH terms
Animals, Biological Clocks, Circadian Rhythm, Darkness, Drosophila, Fourier Analysis, Homozygote, Mice, Inbred C57BL, Molecular Sequence Data, Nuclear Proteins, Phenotype, Transcription Factors, Sequence Deletion, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Mice, Period Circadian Proteins

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