International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 76 - TWO NOVEL ENU-INDUCED CIRCADIAN RHYTHM MUTANTS IN MICE

Siepka SM 1, McGurk R 1, Chen M 1, Marusawa A 1, Olson D 1, Walkowiak J 1, Pinto L 1, Takahashi JS 2

1 Center for Functional Genomics, Northwestern University, Evanston, United States, 2 Howard Hughes Medical Institute, Evanston, United States

In the last decade, tremendous progress has been made in identifying genes and gene products that appear to be key components of the mammalian circadian clock. In mammals, genetic screens for circadian rhythms mutations have been limited in both scale and scope. We are currently engaged in a large-scale ENU mutagensis screen for recessive mutations affecting the nervous system and behavior (http://genome.northwestern.edu/neuro). One of the five domains of primary interest in this project is circadian behavior.

As a pilot study, we conducted a small three-generation recessive mutation screen using BTBR/J mice. Approximately 3600 mice from 217 different mutant pedigrees were screened for abnormalities in circadian locomotor activity. Two of these mutant lines produced mice with altered free running periods. The first mutant, part-time, is a recessive mutation with a free running period approximately 1.5 hours shorter (21.5 hours) than that of wild type mice (23.17 + 0.22 hrs). part-time maps to chromosome 10 and is a new mutant allele of the Cryptochrome1 gene. The second mutant, Overtime, is a semi-dominant mutation with a free running period more than 2.5 hours longer (25.9 hrs) than that of wild type mice. Overtime maps to mouse chromosome 14 and is particularly interesting because it maps to a chromosome where there are no known circadian rhythm genes. The identification and characterization of these new circadian mutants suggest that additional circadian genes remain to be identified.

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