Deficiency in plasma membrane calcium ATPase isoform 2 increases susceptibility to noise-induced hearing loss in mice.
Susceptibility to noise-induced hearing loss (NIHL) is poorly understood at the genetic level. Mice homozygous for a null mutation in the plasma membrane Ca2+-ATPase isoform 2 (PMCA2) gene are deaf (Kozel et al., 1998). PMCA2 is expressed on outer hair cell stereocilia (Furuta et al., 1998). Fridberger et al. (1998) observed that the outer hair cell cytoplasmic Ca2+ concentration rises following acoustic overstimulation. We hypothesized that Pmca2+/- mice may be more susceptible to NIHL. Since the auditory brainstem response (ABR) thresholds of Pmca2+/- mice vary with the presence of a modifier locus (Noben-Trauth et al., 1997), Pmca2+/- mice were outcrossed to normal hearing CAST/Ei mice. The pre-exposure ABR thresholds of the resulting Pmca2+/+ and Pmca2+/- siblings were indistinguishable. Groups of these mice were exposed to varying intensities of broadband noise, and ABR threshold shifts were calculated. Fifteen days following an 8 h, 113 dB noise exposure, the Pmca2+/- mice displayed significant (P < or = 0.0007) permanent threshold shifts at 16 and 32 kHz that were 15 or 25 dB greater than those observed in Pmca2+/+ littermates. Pmca2 may be the first gene with a known mutated protein product that confers increased susceptibility to NIHL.
Kozel
Peter J
PJ
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, OH 45267, USA.
Davis
Rickie R
RR
Krieg
Edward F
EF
Shull
Gary E
GE
Erway
Lawrence C
LC
D000818:Animals; D001309:Auditory Threshold; D000252:Calcium-Transporting ATPases / Q000172:deficiency* / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology; D016057:Evoked Potentials, Auditory, Brain Stem; D014644:Genetic Variation; D006317:Hearing Loss, Noise-Induced / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D013045:Species Specificity
D007527:Isoenzymes; D000252:Calcium-Transporting ATPases