BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.

The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgeni...

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Autores principales:	Giulia Crispino, Giovanni Di Pasquale, Pietro Scimemi, Laura Rodriguez, Fabian Galindo Ramirez, Romolo Daniele De Siati, Rosa Maria Santarelli, Edoardo Arslan, Mario Bortolozzi, John A Chiorini, Fabio Mammano
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7d65068302f431e8428757bfc8a5321
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spelling	oai:doaj.org-article:f7d65068302f431e8428757bfc8a53212021-11-18T06:47:41ZBAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.1932-620310.1371/journal.pone.0023279https://doaj.org/article/f7d65068302f431e8428757bfc8a53212011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21876744/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.Giulia CrispinoGiovanni Di PasqualePietro ScimemiLaura RodriguezFabian Galindo RamirezRomolo Daniele De SiatiRosa Maria SantarelliEdoardo ArslanMario BortolozziJohn A ChioriniFabio MammanoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23279 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giulia Crispino Giovanni Di Pasquale Pietro Scimemi Laura Rodriguez Fabian Galindo Ramirez Romolo Daniele De Siati Rosa Maria Santarelli Edoardo Arslan Mario Bortolozzi John A Chiorini Fabio Mammano BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
description	The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.
format	article
author	Giulia Crispino Giovanni Di Pasquale Pietro Scimemi Laura Rodriguez Fabian Galindo Ramirez Romolo Daniele De Siati Rosa Maria Santarelli Edoardo Arslan Mario Bortolozzi John A Chiorini Fabio Mammano
author_facet	Giulia Crispino Giovanni Di Pasquale Pietro Scimemi Laura Rodriguez Fabian Galindo Ramirez Romolo Daniele De Siati Rosa Maria Santarelli Edoardo Arslan Mario Bortolozzi John A Chiorini Fabio Mammano
author_sort	Giulia Crispino
title	BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
title_short	BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
title_full	BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
title_fullStr	BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
title_full_unstemmed	BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.
title_sort	baav mediated gjb2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf cx26sox10cre mice.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f7d65068302f431e8428757bfc8a5321
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BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.

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