title: Hearing is normal without connexin30.
abstract: Gjb2 and Gjb6, two contiguous genes respectively encoding the gap junction protein connexin26 (Cx26) and connexin 30 (Cx30) display overlapping expression in the inner ear. Both have been linked to the most frequent monogenic hearing impairment, the recessive isolated deafness DFNB1. Although there is robust evidence for the direct involvement of Cx26 in cochlear functions, the contribution of Cx30 is unclear since deletion of Cx30 strongly downregulates Cx26 both in human and in mouse. Thus, it is imperative that any role of Cx30 in audition be clearly evaluated. Here, we developed a new Cx30 knock-out mouse model (Cx30(Δ/Δ)) in which half of Cx26 expression was preserved. Our results show that Cx30 and Cx26 coordinated expression is dependent on the spacing of their surrounding chromosomic region, and that Cx30(Δ/Δ) mutants display normal hearing. Thus, in deaf patients with GJB6 deletion as well as in the previous Cx30 knock-out mouse model, defective Cx26 expression is the likely cause of deafness, and in contrast to current opinion, Cx30 is dispensable for cochlear functions.
authors.affiliation: Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB)/Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 7241/Institut National de la Santé et de la Recherche Médicale (Inserm), U1050, 75231 Paris cedex 05, France.
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Boulay
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: del Castillo
authors.forename: Fabrice
authors.initials: F
authors.lastname: Giraudet
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Hamard
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Paul
authors.initials: P
authors.lastname: Avan
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Salmon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003051:Cochlea / Q000502:physiology; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000235:genetics; D003638:Deafness / Q000235:genetics; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005838:Genotype; D006309:Hearing / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; C100629:Gjb6 protein, mouse; D000072259:Connexin 26; D004247:DNA