PUBLICATION

Identification of a mutation in the Clock1 gene affecting zebrafish circadian rhythms

Authors
Tan, Y., DeBruyne, J., Cahill, G.M., and Wells, D.E.
ID
ZDB-PUB-080630-2
Date
2008
Source
Journal of neurogenetics   22(2): 149-166 (Journal)
Registered Authors
Cahill, Greg
Keywords
Danio rerio, ENU mutagenesis, Locomotor rhymthicity, Melatonin cycles, Radiation hybrid mapping, Positional cloning
MeSH Terms
  • Amino Acid Substitution/genetics
  • Animals
  • CLOCK Proteins
  • Chromosome Mapping
  • Circadian Rhythm/genetics*
  • DNA-Binding Proteins/genetics*
  • Genetic Linkage
  • Genotype
  • Male
  • Melatonin/metabolism
  • Phenotype
  • Pineal Gland/metabolism
  • Point Mutation/genetics*
  • Polymorphism, Genetic/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators/genetics*
  • Zebrafish/genetics*
PubMed
18569451 Full text @ J. Neurogenet.
Abstract
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, Clk1(dg3), 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping