title: Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness.
abstract: Hearing loss is the most widespread sensory disorder, with an incidence of congenital genetic deafness of 1 in 1600 children. For many ethnic populations, the most prevalent form of genetic deafness is caused by recessive mutations in the gene gap junction 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.
authors: Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
authors: Takashi
authors: T
authors: Iizuka
authors: Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
authors: Kazusaku
authors: K
authors: Kamiya
authors: Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 135-8550, Japan.
authors: Satoru
authors: S
authors: Gotoh
authors: Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 135-8550, Japan.
authors: Yoshinobu
authors: Y
authors: Sugitani
authors: Department of Otolaryngology, Teikyo University Chiba Medical Center, Ichihara 299-0111, Japan and.
authors: Masaaki
authors: M
authors: Suzuki
authors: Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 135-8550, Japan, Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, Tsukuba 305-0074, Japan.
authors: Tetsuo
authors: T
authors: Noda
authors: Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 135-8550, Japan, Team for Advanced Development and Evaluation of Human Disease Models, RIKEN BioResource Center, Tsukuba 305-0074, Japan.
authors: Osamu
authors: O
authors: Minowa
authors: Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan, ike@juntendo.ac.jp.
authors: Katsuhisa
authors: K
authors: Ikeda
mesh_terms: D000818:Animals; D003051:Cochlea / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D003638:Deafness / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006309:Hearing; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018743:Perinatal Care
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26