Mutagenesis and Mapping of a Mouse Gene, Clock , Essential for Circadian Behavior

Vitaterna, Martha Hotz; King, David P.; Chang, Anne-Marie; Kornhauser, Jon M.; Lowrey, Phillip L.; McDonald, J. David; Dove, William F.; Pinto, Lawrence H.; Turek, Fred W.; Takahashi, Joseph S.

doi:10.1126/science.8171325

Cited by 1,632Circadian rhythm and melatoninSleep and Wakefulness ResearchSleep and Work-Related Fatigue

Mutagenesis and Mapping of a Mouse Gene, Clock , Essential for Circadian Behavior

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Vitaterna, Martha Hotz, King, David P., Chang, Anne-Marie, Kornhauser, Jon M., Lowrey, Phillip L., McDonald, J. David, Dove, William F., Pinto, Lawrence H. +2 more·1994·Science

DOI 10.1126/science.8171325PMC PMC3839659

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Abstract

In a search for genes that regulate circadian rhythms in mammals, the progeny of mice treated with N-ethyl-N-nitrosourea (ENU) were screened for circadian clock mutations. A semidominant mutation, Clock, that lengthens circadian period and abolishes persistence of rhythmicity was identified. Clock segregated as a single gene that mapped to the midportion of mouse chromosome 5, a region syntenic to human chromosome 4. The power of ENU mutagenesis combined with the ability to clone murine genes by map position provides a generally applicable approach to study complex behavior in mammals.

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The Clock mutant mouse has a lengthened endogenous circadian period.
“The primary genetic model for examining linkage between the circadian and metabolic systems has been the Clock mutant mouse, in which the core circadian gene, Clock, is mutated such that the animal's endogenous circadian period is lengthened (47).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [47]
Genetic and biochemical evidence demonstrates that the bHLH-PAS protein CLOCK is required for the proper maintenance of circadian rhythms in mammals.
“Genetic and biochemical evidence demonstrates that the bHLH-PAS protein CLOCK is required for the proper maintenance of circadian rhythms in mammals.”
From Mop3 is an essential component of the master circadian pacemaker in mammals. (2000) · cites this paper as Vitaterna et al. 1994

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Mutagenesis and mapping of a mouse gene, Clock, essential for circadian …
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Chemical Mutagenesis and Screening for Mouse Mutations with an Altered Rest–Activity Pattern
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Authors: Vitaterna, M. H., King, D. P., Chang, A.-M., Kornhauser, J. M., Lowrey, P. L., McDonald, J. D., Dove, W. F., Pinto, L. H., Turek, F. W., & Takahashi, J. S.
Affiliations: Northwestern University (US)
University of Wisconsin–Madison (US)
ORCID: Vitaterna, Martha Hotz
Chang, Anne-Marie
Dove, William F.
Turek, Fred W.
Takahashi, Joseph S.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1994-04-29
Volume: 264
Issue: 5159
Pages: 719-725
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.8171325
PMC: PMC3839659
OpenAlex: W1992494470
Cited by: 1,632
References: 49
Citations by year: 2026: 17 · 2025: 53 · 2024: 41 · 2023: 39 · 2022: 47 · 2021: 50 · 2020: 58 · 2019: 42 · 2018: 59 · 2017: 57 · 2016: 51 · 2015: 53 · 2014: 66 · 2013: 62 · 2012: 50
FWCI: 22.28
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health (5p30ca007175-36)
National Cancer Institute (P30 CA 07175)
National Institute on Deafness and Other Communication Disorders (T32DC000015)
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK40493)
National Institute of Neurological Disorders and Stroke (T32 NS071040)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords: clock genes, circadian rhythm, circadian activity, N-ethyl-N-nitrosourea mutagenesis, ENU mutagenesis, mouse chromosome 5, human chromosome 4, gene mapping, semi-dominant mutation, circadian period, behavioral genetics
MeSH terms: Animals, Chromosome Mapping, Chromosomes, Human, Pair 4, Circadian Rhythm, Ethylnitrosourea, Female, Genes, Genotype, Humans, Male, Mice, Inbred C57BL, Phenotype, Mutagenesis, Mice

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Mutagenesis and Mapping of a Mouse Gene, Clock , Essential for Circadian Behavior

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