Positional Cloning of the Mouse Circadian Gene

King, David P; Zhao, Yaliang; Sangoram, Ashvin M; Wilsbacher, Lisa D; Tanaka, Minoru; Antoch, Marina P; Steeves, Thomas D.L; Vitaterna, Martha Hotz; Kornhauser, Jon M; Lowrey, Phillip L; Turek, Fred W; Takahashi, Joseph S

doi:10.1016/s0092-8674(00)80245-7

Cited by 1,382Circadian rhythm and melatoninPlant Molecular Biology ResearchLight effects on plants

Positional Cloning of the Mouse Circadian Gene

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King, David P, Zhao, Yaliang, Sangoram, Ashvin M, Wilsbacher, Lisa D, Tanaka, Minoru, Antoch, Marina P, Steeves, Thomas D.L, Vitaterna, Martha Hotz +4 more·1997·Cell

DOI 10.1016/s0092-8674(00)80245-7PMC PMC3815553

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Abstract

We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning approximately 100,000 bp of DNA from which transcript classes of 7.5 and approximately 10 kb arise. Clock encodes a novel member of the bHLH-PAS family of transcription factors. In the Clock mutant allele, an A-->T nucleotide transversion in a splice donor site causes exon skipping and deletion of 51 amino acids in the CLOCK protein. Clock is a unique gene with known circadian function and with features predicting DNA binding, protein dimerization, and activation domains. CLOCK represents the second example of a PAS domain-containing clock protein (besides Drosophila PERIOD), which suggests that this motif may define an evolutionarily conserved feature of the circadian clock mechanism.

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The Clock gene is one of the central components of the circadian machinery.
“This includes the identification of the Clock gene which is one of the central components of the circadian machinery (King et al., 1997).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as King et al., 1997
These CLOCK mutant mice have a point mutation in the CLOCK gene caused by ENU mutagenesis that results in a dominant-negative protein.
“These mice have a point mutation in the CLOCK gene caused by ENU mutagenesis that results in a dominant-negative protein (King et al., 1997).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as King et al., 1997
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 King et al. 1997

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Authors: King, D. P., Zhao, Y., Sangoram, A. M., Wilsbacher, L. D., Tanaka, M., Antoch, M. P., Steeves, T. D. L., Vitaterna, M. H., Kornhauser, J. M., Lowrey, P. L., Turek, F. W., & Takahashi, J. S.
Affiliations: Northwestern University (US)
Corresponding author: Takahashi, Joseph S
ORCID: Wilsbacher, Lisa D
Tanaka, Minoru
Antoch, Marina P
Vitaterna, Martha Hotz
Turek, Fred W
Takahashi, Joseph S
Venue: Cell
Publisher: Elsevier BV
Published: 1997-05
Volume: 89
Issue: 4
Pages: 641-653
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)80245-7
PMC: PMC3815553
OpenAlex: W2054513544
Cited by: 1,382
References: 75
Citations by year: 2026: 16 · 2025: 37 · 2024: 34 · 2023: 21 · 2022: 40 · 2021: 38 · 2020: 48 · 2019: 38 · 2018: 40 · 2017: 45 · 2016: 37 · 2015: 35 · 2014: 41 · 2013: 59 · 2012: 45
FWCI: 28.98
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5921 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation
Howard Hughes Medical Institute
National Institutes of Health (5r37mh039592-12, 5p30hd028048-08)
National Institute of Mental Health (R37 MH 39592)
National Institute of General Medical Sciences (GM 08152, T32GM008152)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30-HD28048)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
Keywords: clock genes, circadian clock, positional cloning, bHLH-PAS transcription factors, PAS domain, exon skipping, splice donor site mutation, circadian clock mechanism, transcription factor dimerization, DNA-binding domain
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Chick Embryo, Chromosome Mapping, Circadian Rhythm, Cloning, Molecular, Dogs, Drosophila, Humans, Molecular Sequence Data, Mutation, RNA, Messenger, Trans-Activators, Conserved Sequence, Sequence Homology, Amino Acid, DNA Primers, DNA, Complementary, Evolution, Molecular, Mice, CLOCK Proteins

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Positional Cloning of the Mouse Circadian Gene

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