The deafwaddler (dfw) mouse is presently a model for recessive sensorineural deafness. Heterozygous mice, however, show variable hearing loss depending on the background and the severity of the dfw allele. The causative mutation affects the Atp2b2 gene encoding the plasma membrane calcium pump PMCA2 (Street, et al., 1998). The ultimate goal of the present study is to evaluate dfw heterozygotes as a model for age-related hearing loss (AHL) and noise-induced hearing loss (NIHL). A partial loss-of-function allele (dfw) and a functional null allele (dfw-J) will be used (Penheiter et al., 2001; Street et al., 1998). Both alleles are maintained in a CBA/CaJ background, the 'gold standard' for hearing in mice. We will measure hearing loss using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. The organ of Corti will also be examined microscopically in order to correlate histopathology with functional measurements. An additional aim is to investigate a potential genetic interaction between the dfw and waltzer (v) loci by examining the susceptibility to NIHL in trans-heterozygotes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DC005861-04
Application #
6998919
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2003-01-01
Project End
2006-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
4
Fiscal Year
2006
Total Cost
$34,105
Indirect Cost
Name
University of Washington
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
McCullough, Brendan J; Adams, Joe C; Shilling, Dustin J et al. (2007) 3p-- syndrome defines a hearing loss locus in 3p25.3. Hear Res 224:51-60