International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 5 - IDENTIFICATION OF THE BASIC LEUCINE ZIPPER AND W2 DOMAINS 2, BZW2, AS A PUTATIVE CIRCADIAN QUANTATIVE TRAIT GENE

Pletcher M T
The Genomics Institute of the Novartis Research Foundation

Co-Authors: Hogenesch J, Kay S, Wiltshire T
Institutions: The Genomics Institute of the Novartis Research Foundation

Recombinant inbred (RI) mice have been used for the mapping of genes affecting multiple and widely varying phenotypes without requiring new genotyping data for each mapping exercise. This property was exploited in the investigation of quantitative trait loci (QTL) affecting circadian behavior by applying the ratio of light:dark activity rates (Toth et al., Behavioral Genetics, 1999) in 13 CxB RI strains to a 1428 marker, high resolution physical map of the strain distribution patterns of these mice. A high phenotype/genotype correlation was found for a 11 MB region on mouse chromosome 12. Using the gene expression database GeneAtlas (http://expression.gnf.org/circadian), 3 genes were identified within this region as being expressed in the suprachiasmatic nucleus (SCN) in a cyclical manner consistent with a role in circadian locomotor activity. One of these genes, Bzw2, contained a strain specific amino acid difference in its coding region. Preliminary cell culture experiments have shown that the C57BL6/J-derived clone of Bzw2 acts antagonistically on the expression of Sui1 while the BALB/cByJ version has no effect. Consistant with these findings, the GeneAtlas shows that Sui1 also displays circadian cycling in the SCN but in the opposite phase as Bzw2. Work is currently underway to confirm and extend these results


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