The objective of this proposal is to isolate and characterize the gene responsible for autosomal recessive deafness in the mouse pirouette mutant. Preliminary work has localized the gene to a 5 cM region of mouse chromosome 5 that is syntenic to 4p14-q12. Here Dr. Kohrman proposes to refine the map of the pirouette locus, evaluate candidate genes, construct a contig of the nonrecombinant region, and identify genes within the region by exon trapping and cDNA selection. Once a likely gene has been identified, it will be compared in structure and expression in control and mutant mice, and expression of the gene will be examined by ribonuclease protection, RT-PCR, and in situ hybridization. Finally, the human homolog will be cloned, sequenced, and chromosomally mapped in order to generate reagents for mutation detection in human patients.
| Odeh, Hana; Hunker, Kristina L; Belyantseva, Inna A et al. (2010) Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse. Am J Hum Genet 86:148-60 |
| Odeh, Hana; Hagiwara, Nobuko; Skynner, Michael et al. (2004) Characterization of two transgene insertional mutations at pirouette, a mouse deafness locus. Audiol Neurootol 9:303-14 |
