The t complex, located on the proximal end of chromosome 17, comprises approximately 1 percent of the mouse genome and as such, it is estimated to contain on the order of 100 genes. The goal of the proposed project is to make a series of deletions within the t complex that will be used in combination to uncover genes involved in development. Specifically, two sets of ten to fifteen deletions will be made around the Sod2 and D17Leh94 loci; deficiencies in this portion of the genome will uncover the hybrid sterility gene Hst1, as well as several regions known to be required for correct development. Genes within the t complex have been difficult to clone since most mutations arose in partial t haplotypes that contain inversions with respect to wild-type, thereby preventing the fine structure mapping that usually allows determination of a gene's location. The generation of relatively small, overlapping deletions whose breakpoints are known will enable the identification of the physical location of these genes in a short amount of time; preliminary characterization and initial steps towards cloning one or more of these genes will be undertaken. Through the creation of a set of overlapping deletions in mice, which are then crossed together to form compound heterozygotes, a functional map of approximately half of the t complex will be generated.
| Browning, V L; Chaudhry, S S; Planchart, A et al. (2001) Mutations of the mouse Twist and sy (fibrillin 2) genes induced by chemical mutagenesis of ES cells. Genomics 73:291-8 |
