A novel mode of off-frequency hearing as a result of defective outer hair cells hair bundles unveiled by Nherf1-/- mice

Nherf1, a PDZ-domain-containing protein, was identified in the hair bundle in differentiating outer hair cells (OHCs). Nherf1-/- mice showed apparently mild hearing-threshold elevations at mid/high sound frequencies, associated to OHC hair-bundle shape anomalies, prominent in the basal cochlea. This mild impact on hearing sensitivity was discordant with the finding of almost non-responding OHCs in the basal cochlea as assessed by distortion-product otoacoustic emissions and cochlear microphonic potentials. Unlike normal mice, responses of Nherf1-/- mice to high-frequency test tones were not masked by tones of neighboring frequencies. Efficient masker tones displayed unusual characteristics: maximal efficiency at lower frequencies (up to two octaves lower than the test tone), and at low levels (up to 25 dB below test-tone level). This, and the relative growth of the masker and test tones, suggests that mid-high frequency tones of moderate intensity are detected off-frequency, in the functionally unaffected...