Deficiency in plasma membrane calcium ATPase isoform 2 increases susceptibility to noise-induced hearing loss in mice

摘要: Abstract Susceptibility to noise-induced hearing loss (NIHL) is poorly understood at the genetic level. Mice homozygous for a null mutation in plasma membrane Ca2+-ATPase isoform 2 (PMCA2) gene are deaf (Kozel et al., 1998). PMCA2 expressed on outer hair cell stereocilia (Furuta Fridberger al. (1998) observed that cytoplasmic Ca2+ concentration rises following acoustic overstimulation. We hypothesized Pmca2+/− mice may be more susceptible NIHL. Since auditory brainstem response (ABR) thresholds of vary with presence modifier locus (Noben-Trauth 1997), were outcrossed normal CAST/Ei mice. The pre-exposure ABR resulting Pmca2+/+ and siblings indistinguishable. Groups these exposed varying intensities broadband noise, threshold shifts calculated. Fifteen days an 8 h, 113 dB noise exposure, displayed significant (P≤0.0007) permanent 16 32 kHz 15 or 25 greater than those littermates. Pmca2 first known mutated protein product confers increased susceptibility