title: Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential.
abstract: The gap junction protein connexin30 (Cx30) is expressed in a variety of tissues that include epithelial and mesenchymal structures of the inner ear. We generated Cx30 (Gjb6) deficient mice by deletion of the Cx30 coding region. Homozygous mutants (Cx30((-/-))) were born at the expected Mendelian frequency, developed normally and were fertile. However, they exhibit a severe constitutive hearing impairment. From the age of hearing onset, these mice lack the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea, i.e. the endocochlear potential, which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium starts to degenerate by cell apoptosis. This degeneration process is likely to account for the concomitant decrease of the endolymphatic potassium concentration and the aggravation of the hearing loss in adult Cx30((-/-)) mice. The Cx30 ((-/-)) phenotype thus reveals the critical role of Cx30 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. The Cx30 deficient mice may represent a valuable model to study the mechanism of the hearing loss in human patients carrying a homozygous deletion of the CX30 gene (del Castillo et al., 2002, New Engl. J. Med., 346, 243-249).
authors.affiliation: Institut für Genetik, Abteilung Molekulargenetik, Universität Bonn, Bonn, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Teubner
authors.forename: Vincent
authors.initials: V
authors.lastname: Michel
authors.forename: Jörg
authors.initials: J
authors.lastname: Pesch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lautermann
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Salmon
authors.forename: Goran
authors.initials: G
authors.lastname: Söhl
authors.forename: Klaus
authors.initials: K
authors.lastname: Jahnke
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.forename: Claus
authors.initials: C
authors.lastname: Herberhold
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000483:Alleles; D000818:Animals; D003051:Cochlea / Q000378:metabolism / Q000502:physiology*; D000075302:Connexin 30; D017630:Connexins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000075302:Connexin 30; D017630:Connexins; C491020:GJB6 protein, human; C100629:Gjb6 protein, mouse