The goal of the research proposed is to delineate the pathogenesis of the nonsyndromic autosomal dominant deafness disorder DFNA9 and to elucidate the functional role of the novel gene COCH in maintaining proper hearing and balance. This investigation will center upon the production and study of a mouse model for DFNA9. The mouse Coch gene has been cloned and characterized and provides an excellent reagent for this study. Three missense mutations that have been identified in patients with DFNA9 will be introduced into genomic subclones of the mouse Coch gene using targeted mutagenesis, and homologous recombination will be utilized to introduce the individual mutations into mouse embryonic stem (ES) cells. Mouse lines carrying the mutated Coch gene will then be produced from ES cells and evaluated. The pattern of mutant Coch expression will be determined in mice by RNA and protein analysis, including gross histopathological studies, in situ hybridization, and immunohistochemistry with a Coch-specific antibody. Mice will be extensively analyzed for hearing ability by a number of behavioral tests and by auditory brainstem threshold analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DC000434-01
Application #
6135075
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Sklare, Dan
Project Start
2000-07-01
Project End
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$32,416
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115