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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DC003049-03
Application #
2749257
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1996-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Genetics
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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