The Role of PMCA2 in Hearing Loss

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18. GOALS FOR FELLOWSHIP TRAINING AND CAREER NAME (Last, first, middle initial) McCullough, Brendan J. INSTITUTION MENTOR Stanford University Dr. Thomas Schwarz University of Washington Dr. Bruce Tempel University of Washington N/A INSTITUTION/COMPANY SUPERVISOR/EMPLOYER The knowledge and experience gained under this fellowship will provide me with the skills necessary to investigate detailed mechanisms associated with human disease. The first three years of this award will be devoted to basic science research investigating age-related hearing loss and noise-induced hearing loss in the deafwaddler mouse. During this time, I intend to develop a scientific approach to experimental questions and learn techniques for examining those questions. Techniques I will use include genetics, functional measurements of hearing and confocal microscopy. My fourth and final year of this fellowship will be spent in the clinic as a third year medical student, preparing me to be a physician. Together, the in-depth nature of basic science research and the broad knowledge of medicine will prepare me for a career as a physician-scientist. 19. NAME AND DEGREE(S) Bruce L Tempel, Phi3 20. POSITION/RANK Professor, Departments of Otolaryngology-HNS and Pharmacology 21. RESEARCH INTERESTS/AREAS Auditory signalling; neuronal hyperactivity; auditory neurogenetics ; |=:_-_]*_1:ie,]_i, -J:;[e]-jo],,.'_.l 22, DESCRIPTION (Do not exceed space provided) 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 2J) 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. PHS 416-1 (Rev, 12/98) Form Page 2 BB cc Individual NRSA Application Table of Contents ========================================Section End===========================================