Downregulation of otospiralin, a novel inner ear protein, causes hair cell degeneration and deafness.

Mesenchymal nonsensory regions of the inner ear are important structures surrounding the neurosensory epithelium that are believed to participate in the ionic homeostasis of the cochlea and vestibule. We report here the discovery of otospiralin, an inner ear-specific protein that is produced by fibrocytes from these regions, including the spiral ligament and spiral limbus in the cochlea and the maculae and semicircular canals in the vestibule. Otospiralin is a novel 6.4 kDa protein of unknown function that shares a protein motif with the gag p30 core shell nucleocapsid protein of type C retroviruses. To evaluate its functional importance, we downregulated otospiralin by cochlear perfusion of antisense oligonucleotides in guinea pigs. This led to a rapid threshold elevation of the compound action potentials and irreversible deafness. Cochlear examination by transmission electron microscopy revealed hair cell loss and degeneration of the organ of Corti. This demonstrates that otospiralin is essential for the survival of the neurosensory epithelium.