Effects of PMCA2 mutation on DPOAE amplitudes and latencies in deafwaddlermice

The deafwaddler (dfw) mouse mutant is caused by a spontaneous mutation in t he gene that encodes a plasma membrane Ca2+ 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) ampl itudes and latencies were examined in control mice, deafwaddler mutants: an d controls treated with the drug furosemide, Furosemide causes a transient reduction of DPOAEs (Mills et al., 1993. J. Acoust. Sec. 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 ampli tude and phase were measured as a function of f(2)/f(1) ratio. These data w ere converted into waveforms using inverse fast Fourier transform, and thei r average latency was used to estimate DPOAE group delay. Homozygous deafwa ddlers did not produce DPOAEs. Heterozygous deafwaddlers (+/dfw) had increa sed DPOAE thresholds and reduced amplitudes at high frequencies, compared t o controls. To the extent that DPOAEs depend on functional outer hair cells (OHCs), abnormal DPOAEs in +/dfw mice suggest that PMCA2 is important for OI-IC function at high frequencies. Similar to the effects of furosemide, t he mutation reduced DPOAEs for low-level stimuli; in contrast to furosemide , the mutation altered DPOAEs elicited by high levels. (C) 2001 Elsevier Sc ience B.V. All rights reserved.