Otoferlin Expression and Distribution in the Developing and Mature Rat Cochlea

Abstract

Otoferlin (OTOF) is a multi C2 domain transmembrane protein expressed in the sensory inner hair cells of the cochlea, whose mutation underlies a form of an autosomal recessive, non-syndromic prelingual deafness, DFNB9. Otoferlin is proposed to act as a calcium sensor that regulates synaptic vesicle exocytosis in cochlear inner hair cells. Current research reveals a role for otoferlin in priming and fusion of synaptic vesicles during sound encoding. This study postulates that OTOF is developmentally regulated in the rat cochlea. OTOF expression was measured by quantitative real-time RT-PCR and immunohistochemistry in the postnatal (P0-P21) and adult (P50) rat cochlea. Our experiments demonstrated that maximum OTOF expression was observed at birth and maintained at a high level until P6, followed by a decline in expression until P12 (the onset of hearing), when it reached minimum level. The expression level increased again after the onset of hearing and reached the adult level at P50. OTOF immunoreactivity was distributed differentially during development. OTOF immunoreactivity was found in both types of sensory hair cells, Kolliker’s organ and spiral ganglion neurons in the pre-hearing period (P0-P9), but was limited to the organ of Corti in the post-hearing period (P12-P50). In the adult cochlea, discrete membrane-bound OTOF immunolabelling was observed exclusively in the inner hair cell lateral wall in the modiolar (neural) region. This differential spatial and temporal expression of OTOF in cochlear tissues during development may reflect differential roles of this synaptic protein in the cochlea before and after the onset of hearing.