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The mouse Clock locus: sequence and comparative analysis of 204 kb from mouse chromosome 5
L D Wilsbacher1, A M Sangoram, M P Antoch
1Howard Hughes Medical Institute, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Genome Research
|December 16, 2000
Summary
Researchers sequenced a 204-kb mouse chromosome region, identifying the complete Clock and Tpardl genes. This genomic region is crucial for regulating circadian rhythms and rescuing Clock mutant phenotypes.
Area of Science:
- Genomics
- Chronobiology
- Molecular Biology
Background:
- The Clock gene, a bHLH-PAS transcription factor, is essential for regulating circadian rhythms in mice.
- Previous work involved cloning the Clock gene in mouse and human using various molecular and behavioral techniques.
- Bacterial artificial chromosome (BAC) clones were utilized in prior shotgun sequencing efforts.
Purpose of the Study:
- To report the finished sequence of a 204-kb region on mouse chromosome 5.
- To identify all genes within this specific genomic region.
- To perform comparative genomic analysis with the syntenic human chromosome region and functionally characterize the Clock gene locus.
Main Methods:
- Shotgun sequencing of bacterial artificial chromosome (BAC) clones.
- Finished genomic sequencing of a 204-kb mouse chromosome region.
- Comparative genomic sequence analysis between mouse and human syntenic regions.
- Generation of a new BAC transgenic mouse line for phenotypic rescue experiments.
Main Results:
- The 204-kb sequenced region contains the complete loci for the Clock and Tpardl genes and the 3' partial locus of the Neuromedin U gene.
- Sequence analysis suggests the presence of two novel, previously unidentified genes within this region.
- Comparative analysis with human chromosome 4 reveals syntenic relationships.
- A BAC transgenic line demonstrated that a genomic region of no more than 120 kb, flanking the 3' end of the Clock gene, is sufficient to rescue the Clock mutant phenotype.
Conclusions:
- The complete genomic sequence of the 204-kb mouse chromosome 5 region provides a comprehensive resource for understanding circadian gene regulation.
- The identified Clock and Tpardl gene loci, along with potential novel genes, offer insights into the genetic architecture of circadian timing.
- The functional data from the BAC transgenic line precisely defines the minimal genomic region required for Clock gene function, crucial for future genetic studies and therapeutic development.