Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness

Hearingloss isthe most widespread sensory disorder, withan incidenceof congenital genetic deafnessof 1 in 1600children. For manyethnicpopulations,themostprevalentformofgeneticdeafnessiscausedbyrecessivemutationsinthegenegapjunction protein, beta 2, 26 kDa (GJB2), which is also known as connexin 26 (Cx26). Despite this knowledge, existing treatment strategies do not completely recover speech perception. Here we used a gene delivery system to rescue hearing in a mouse model of Gjb2 deletion. Mice lacking Cx26 are characterized by profound deafness from birth and improper development of cochlear cells. Cochlear delivery of Gjb2 using an adeno-associated virus significantly improved the auditory responses and development of the cochlear structure. Using gene replacement to restore hearing in a new mouse model of Gjb2-related deafness may lead to the development of therapies for human hereditary deafness.