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.