The strategy to gain hearing ability of the deaf model mouse by injecting into the cochlea

点击翻译按钮获取中文摘要

Hereditary deafness affects about 1 in 2,000 children and mutations in the gap junction beta 2 protein (GJB2) gene, cording the gap junction, are the major cause in various ethnic groups, which require normal gene transfe r in the early developmental stage to prevent deafness. Mice present an ideal model for inner ear gene therapy. In order to establish the fundamental therapy of congenital deafness, we generated targeted disruption of mouse Gjb2 gene using Cre recombinase controlled by P0. Using this animal model, we examined the potential of gene therapy in the inner ear, using the homozygous mutant mice and the heterozygous mutant mice. Adeno -associated virus vectors (AAV) carrying Gjb2 gene were injected into the scala tympani through the round window of the cochlea of the homozygous mutant adult mice. The expression of Cx26 was observed in the fibrocytes of the spiral ligament and spiral limbus, but was not seen in the supporting cells and failed to improve the hearing ability. However, we succeed in gene introduction to the supporting cells of neonatal mice without hearing loss using AAV. The present study will present the preliminary data regarding introduction of the virus vector into the Gjb2 knockout mouse at the neonatal stage.