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In vivo genetic manipulation of inner ear connexin expression by bovine adeno-associated viral vectors.
Crispino, Giulia; Galindo Ramirez, Fabian; Campioni, Matteo; Zorzi, Veronica; Praetorius, Mark; Di Pasquale, Giovanni; Chiorini, John A; Mammano, Fabio.
Afiliación
  • Crispino G; Venetian Institute of Molecular Medicine, Foundation for Advanced Biomedical Research, Padua, Italy.
  • Galindo Ramirez F; Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, Italy.
  • Campioni M; Venetian Institute of Molecular Medicine, Foundation for Advanced Biomedical Research, Padua, Italy.
  • Zorzi V; Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, Italy.
  • Praetorius M; Physiology Institute, Autonomous University of Puebla, Puebla, Mexico.
  • Di Pasquale G; Venetian Institute of Molecular Medicine, Foundation for Advanced Biomedical Research, Padua, Italy.
  • Chiorini JA; Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, Italy.
  • Mammano F; Department of Biochemistry and Biotechnology, University of Pavia, Pavia, Italy.
Sci Rep ; 7(1): 6567, 2017 08 04.
Article en En | MEDLINE | ID: mdl-28779115
We have previously shown that in vitro transduction with bovine adeno-associated viral (BAAV) vectors restores connexin expression and rescues gap junction coupling in cochlear organotypic cultures from connexin-deficient mice that are models DFNB1 nonsyndromic hearing loss and deafness. The aims of this study were to manipulate inner ear connexin expression in vivo using BAAV vectors, and to identify the optimal route of vector delivery. Injection of a BAAV vector encoding a bacterial Cre recombinase via canalostomy in adult mice with floxed connexin 26 (Cx26) alleles promoted Cre/LoxP recombination, resulting in decreased Cx26 expression, decreased endocochlear potential, increased hearing thresholds, and extensive loss of outer hair cells. Injection of a BAAV vector encoding GFP-tagged Cx30 via canalostomy in P4 mice lacking connexin 30 (Cx30) promoted formation of Cx30 gap junctions at points of contacts between adjacent non-sensory cells of the cochlear sensory epithelium. Levels of exogenous Cx30 decayed over time, but were still detectable four weeks after canalostomy. Our results suggest that persistence of BAAV-mediated gene replacement in the cochlea is limited by the extensive remodeling of the organ of Corti throughout postnatal development and associated loss of non-sensory cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Cóclea / Conexinas / Parvovirinae / Sordera / Vectores Genéticos / Oído Interno Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Cóclea / Conexinas / Parvovirinae / Sordera / Vectores Genéticos / Oído Interno Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido