A murine model for the del(GJB6-D13S1830) deletion recapitulating the phenotype of human DFNB1 hearing impairment: generation and functional and histopathological study
María Domínguez-Ruiz,
Silvia Murillo-Cuesta,
Julio Contreras,
Marta Cantero,
Gema Garrido,
Belén Martín-Bernardo,
Elena Gómez-Rosas,
Almudena Fernández,
Francisco J. del Castillo,
Lluís Montoliu,
Isabel Varela-Nieto,
Ignacio del Castillo
Affiliations
María Domínguez-Ruiz
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS
Silvia Murillo-Cuesta
Institute for Biomedical Research “Sols-Morreale”, Spanish National Research Council-Autonomous University of Madrid
Julio Contreras
Institute for Biomedical Research “Sols-Morreale”, Spanish National Research Council-Autonomous University of Madrid
Marta Cantero
Department of Molecular and Cellular Biology, National Centre for Biotechnology (CNB-CSIC)
Gema Garrido
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS
Belén Martín-Bernardo
Institute for Biomedical Research “Sols-Morreale”, Spanish National Research Council-Autonomous University of Madrid
Elena Gómez-Rosas
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS
Almudena Fernández
Department of Molecular and Cellular Biology, National Centre for Biotechnology (CNB-CSIC)
Francisco J. del Castillo
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS
Lluís Montoliu
Department of Molecular and Cellular Biology, National Centre for Biotechnology (CNB-CSIC)
Isabel Varela-Nieto
Institute for Biomedical Research “Sols-Morreale”, Spanish National Research Council-Autonomous University of Madrid
Ignacio del Castillo
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS
Abstract Inherited hearing impairment is a remarkably heterogeneous monogenic condition, involving hundreds of genes, most of them with very small ( 90 dB SPL) that correlates with specific structural abnormalities in the cochlea. We show that Gjb2 expression is nearly abolished and its protein product, Cx26, is nearly absent all throughout the cochlea, unlike previous conditional knockouts in which Gjb2 ablation was not obtained in all cell types. The Dfnb1 em274 model recapitulates the clinical presentation of patients harbouring the del(GJB6-D13S1830) variant and thus it is a valuable tool to study the pathological mechanisms of DFNB1 and to assay therapies for this most frequent type of human ARNSHI.
