Expression of the otoferlin gene is not detected in these mutant mice, indicating that this missense mutation has a severe effect on the stability of the protein and potentially its localization. Auditory brainstem response analysis demonstrated that mice homozygous for the missense mutation are profoundly deaf, consistent with an essential role for otoferlin in inner hair cell neurotransmission. Vestibular-evoked potentials of mutant mice, however, is equivalent to those of wildtype mice, indicating that otoferlin is unnecessary for vestibular function even though it is highly expressed in both vestibular and cochlear hair cells.
Wright et al. found multiple reasons for failed neurotransmission from hair cells, despite normal tonotopic organization. The volume of the ventral cochlear nuclei is smaller than normal by nearly half, the auditory nerve is approximately half the normal thickness, the end bulbs of Held are fewer in number, wispier, and less branched than normal, and some of the axons leading to them are thinner. The bushy cells are contacted by slightly more nerve fibers in mutants (average 2.6) then in hearing controls (average 2.0) and the spontaneous miniature excitatory postsynaptic currents are 24% larger in mutants, despite occurring with similar frequencies and with similar shapes to those of hearing controls.
