Effects of PMCA2 mutation on DPOAE amplitudes and latencies in deafwaddler mice.
The deafwaddler (dfw) mouse mutant is caused by a spontaneous mutation in the gene that encodes a plasma membrane Ca(2+) ATPase (type 2), PMCA2 (Street et al., 1998. Nat. Genet. 19, 390-394), which is expressed in cochlear and vestibular hair cells. Distortion product otoacoustic emission (DPOAE) amplitudes and latencies were examined in control mice, deafwaddler mutants, and controls treated with the drug furosemide. Furosemide causes a transient reduction of DPOAEs (Mills et al., 1993. J. Acoust. Soc. Am. 94, 2108-2122). We wanted to determine whether DPOAEs obtained in furosemide-treated mice were similar or different from results obtained in +/dfw mice. DPOAE amplitude and phase were measured as a function of f(2)/f(1) ratio. These data were converted into waveforms using inverse fast Fourier transform, and their average latency was used to estimate DPOAE group delay. Homozygous deafwaddlers did not produce DPOAEs. Heterozygous deafwaddlers (+/dfw) had increased DPOAE thresholds and reduced amplitudes at high frequencies, compared to controls. To the extent that DPOAEs depend on functional outer hair cells (OHCs), abnormal DPOAEs in +/dfw mice suggest that PMCA2 is important for OHC function at high frequencies. Similar to the effects of furosemide, the mutation reduced DPOAEs for low-level stimuli; in contrast to furosemide, the mutation altered DPOAEs elicited by high levels.
Konrad-Martin
D
D
Department of Speech and Hearing Sciences, University of Washington, Seattle 98195, USA. konradd@boystown.org
Norton
S J
SJ
Mascher
K E
KE
Tempel
B L
BL
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D027682:Cation Transport Proteins; D003638:Deafness / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D005665:Furosemide / Q000633:toxicity; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009154:Mutation; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D053499:Plasma Membrane Calcium-Transporting ATPases
D027682:Cation Transport Proteins; D005665:Furosemide; D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse; D000252:Calcium-Transporting ATPases