Identification of a Mutation in the Clock1 Gene Affecting Zebrafish Circadian Rhythms

As part of an ongoing program to identify genes involved in maintaining circadian rhythms of zebrafish, 6,500 mutagenized genomes were screened for dominant mutants affecting circadian locomotor activity. Molecular analysis of one of these mutant lines, Clk1dg3, revealed an I254N mutation in the PAS...

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Bibliographic Details
Published in:Journal of neurogenetics 2008, Vol.22 (2), p.149-166
Main Authors: Tan, Ying, DeBruyne, Jason, Cahill, Gregory M., Wells, Dan E.
Format: Article
Language:English
Subjects:
Amino Acid Substitution - genetics
Animals
Chromosome Mapping
Circadian Rhythm - genetics
CLOCK Proteins
Danio rerio
DNA-Binding Proteins - genetics
ENU mutagenesis
Genetic Linkage
Genotype
Locomotor rhymthicity
Male
Melatonin - metabolism
Melatonin cycles
Phenotype
Pineal Gland - metabolism
Point Mutation - genetics
Polymorphism, Genetic - genetics
Positional cloning
Radiation hybrid mapping
Reverse Transcriptase Polymerase Chain Reaction
Trans-Activators - genetics
Zebrafish - genetics
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Summary:As part of an ongoing program to identify genes involved in maintaining circadian rhythms of zebrafish, 6,500 mutagenized genomes were screened for dominant mutants affecting circadian locomotor activity. Molecular analysis of one of these mutant lines, Clk1dg3, revealed an I254N mutation in the PAS domain of the Clock1 protein. This isoleucine is tightly conserved in the Clock genes of several different species, and the I254N was not seen in any of the wild-type zebrafish population tested. Analysis of circadian activity rhythms as well as melatonin rhythms in homozygotes revealed the biological clock runs with a shortened period. The effect of this Clock1 mutation was characterized in vitro using a cell culture system where it appears to enhance the transactivation ability of the I254N Clock1 protein compared with that of the normal gene product.
ISSN:0167-7063
1563-5260
DOI:10.1080/01677060802049738