Cited by 1,907Circadian rhythm and melatoninSleep and Work-Related FatigueNonlinear Dynamics and Pattern Formation

Resetting central and peripheral circadian oscillators in transgenic rats

Yamazaki, Shin, Numano, Rika, Abe, Michikazu, Hida, Akiko, Takahashi, Ri-ichi, Ueda, Masatsugu, Block, Gene D., Sakaki, Yoshiyuki +2 more·2000·Science

Abstract

In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.

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Crossref · 10.1126/science.288.5466.682

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Authors
Yamazaki, S., Numano, R., Abe, M., Hida, A., Takahashi, R.-I., Ueda, M., Block, G. D., Sakaki, Y., Menaker, M., & Tei, H.
Affiliations
  • University of Virginia (US)
  • Institute of Medical Science, The University of Tokyo (JP)
  • Y.S. New Technology Institute Inc., 519 Shimoishibashi, Ishibashi-machi, Tochigi, 329-0500, Japan.
Corresponding author
  • Yamazaki, Shin
  • Numano, Rika
  • Abe, Michikazu
  • Menaker, Michael
  • Tei, Hajime
Venue
Science
Published
2000-04-28
Volume
288
Issue
5466
Pages
682-685
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2035809873
Cited by
1,907
References
16
Citations by year
2026: 34 · 2025: 51 · 2024: 71 · 2023: 53 · 2022: 81 · 2021: 65 · 2020: 81 · 2019: 65 · 2018: 70 · 2017: 62 · 2016: 76 · 2015: 60 · 2014: 82 · 2013: 97 · 2012: 79
FWCI
30.78
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (R01MH056647, MH 56647)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Physical Sciences › Computer Science › Computer Networks and Communications › Nonlinear Dynamics and Pattern Formation
Keywords
circadian clock, suprachiasmatic nucleus, peripheral circadian oscillators, luciferase reporter, transgenic rats, circadian entrainment, phase resetting, locomotor rhythm, liver, lung, skeletal muscle, circadian pacemaker
MeSH terms
Animals, Biological Clocks, Circadian Rhythm, Darkness, Light, Liver, Luciferases, Lung, Male, Motor Activity, Nuclear Proteins, Promoter Regions, Genetic, Suprachiasmatic Nucleus, Genes, Reporter, Muscle, Skeletal, Cell Cycle Proteins, Animals, Genetically Modified, Culture Techniques, Mice, Rats, Period Circadian Proteins

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