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

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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, Menaker, Michael, Tei, Hajime·2000·Science

DOI 10.1126/science.288.5466.682

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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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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
ORCID: Yamazaki, Shin
Numano, Rika
Block, Gene D.
Tei, Hajime
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2000-04-28
Volume: 288
Issue: 5466
Pages: 682-685
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.288.5466.682
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 › Physics and Astronomy › Statistical and Nonlinear Physics › 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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Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

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