Virally Mediated Connexin 26 Expression in Postnatal Scala Media Significantly and Transiently Preserves Hearing in Connexin 30 Null Mice

• Type of Material: Article
• Authors: Li Zhang, Emory University; Wenwen Wang, Huazhong University of Science and Technology; Sun Myoung Kim, Emory University; Jianjun Wang, Emory University; Binfei Zhou, Emory University; Weijia Kong, Huazhong University of Science and Technology; James Zheng, Emory University; Xi Lin, Emory University
• Language: English
• Date: 2022-04-27
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Zhang, Wang, Kim, Wang, Zhou, Kong, Zheng and Lin.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fcell.2022.900416
• Title of Journal or Parent Work: Frontiers in Cell and Developmental Biology
• Volume: 10
• Start Page: 900416
• End Page: 900416
• Grant/Funding Information: This study was supported by grants to XL from the National Institute on Deafness and other Communication Disorders (R21DC017272 and RO1 DC014496) and by grant to WW from the National Natural Science Foundation of China (Nos. 81800914).
• Keywords: hearing sensitivity; mouse; scala media; virus; cochlea; connexin; gene therapy
• Research Categories: Biology, Cell

Abstract

Non-sensory cells in the sensory epithelium of the cochlea are connected extensively by gap junctions. Functionally null mutations in GJB6 (encoding Cx30) cause hearing loss in humans. In this study, we injected AAV1-CB7-Gjb2 into the scala media between P0-2 in the cochlea of Gjb6−/− mice. The injection increased Cx26 expression and significantly preserved auditory functions. However, the hearing preservation gradually declined and essentially disappeared 3 months after the injections. In contrast, the morphological preservation was still significant at 3 months post-injection. We found that the expression of Cx26, at both the mRNA and protein levels, showed substantial decreases during the 3-month period. Curiously, treatments by injecting AAV1-CB7-Gjb6 with the identical approach failed to yield any hearing preservation. Our results demonstrated the first successful cochlear gene therapy treatment in mouse models by virally expressing a companion gene of Gjb6.