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Abstract Background The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. Results Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. Conclusions These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

Abstract Background Auditory function and cochlear morphology have previously been described in a porcine model with spontaneous WS2-like phenotype. In the present study, cochlear histopathology was further investigated in the inner ear of the developing spontaneous deafness pig. Results We found that the stria vascularis transformed into a complex tri-laminar tissue at embryonic 85 days (E85) in normal pigs, but not in the MITF−/− pigs. As the neural crest (NC) of cochlea was derived by melanocytes. MITF mutation caused failure of development of melanocytes which caused a subsequent collapse of cochlear duct and deficits of the epithelium after E100. Furthermore, the spiral ganglion neurons of cochlea in the MITF−/− pigs began to degenerate at postnatal 30 days (P30). Thus, our histopathological results indicated that the malformation of the stria vascularis was a primary defect in MITF−/− induced WT pigs which was resulted from the loss of NC-derived melanocytes. Subsequently, the cochleae underwent secondary degeneration of the vestibular organs. As the degeneration of spiral ganglion neurons happened after P30, it suggests that WS patients should be considered as candidates for cochlear implant. Conclusions Our porcine model of MITF-M mutation may provide a crucial animal model for cochlear implant, cell therapy in patients with congenital hereditary hearing loss.