Drug discovery for hereditary deafness targeting cochlear gap junction

Abstract

Mutation of the Gap Junction Beta 2 gene (GJB2) is the most frequent cause of hereditary deafness worldwide. GJB2 encodes connexin (Cx) 26, a component in cochlear gap junction. We have demonstrated that the drastic disruption of gap junction plaque (GJP) macromolecular complex composed of Cx26 and Cx30 are critical pathogenesis and it could be a target for drug discovery. By differentiation of iPS cells, we generated the Cx26-expressiong cells with large gap junction plaque as cochlear cells. Furthermore, these cells from CX26-deficient mice recapitulated the drastic disruption of GJPs observed in the cochlea. These in vitro models should be useful for establishing drug screening that target GJB2-related hearing loss.