title: Postnatal development of the organ of Corti in dominant-negative Gjb2 transgenic mice.
abstract: Hereditary hearing loss is one of the most prevalent inherited human birth defects, affecting one in 2000. A strikingly high proportion (50%) of congenital bilateral nonsyndromic sensorineural deafness cases have been linked to mutations in the GJB2 coding for the connexin26. It has been hypothesized that gap junctions in the cochlea, especially connexin26, provide an intercellular passage by which K(+) are transported to maintain high levels of the endocochlear potential essential for sensory hair cell excitation. We previously reported the generation of a mouse model carrying human connexin26 with R75W mutation (R75W+ mice). The present study attempted to evaluate postnatal development of the organ of Corti in the R75W+ mice. R75W+ mice have never shown auditory brainstem response waveforms throughout postnatal development, indicating the disturbance of auditory organ development. Histological observations at postnatal days (P) 5-14 were characterized by i) absence of tunnel of Corti, Nuel's space, or spaces surrounding the outer hair cells, ii) significantly small numbers of microtubules in inner pillar cells, iii) shortening of height of the organ of Corti, and iv) increase of the cross-sectional area of the cells of the organ of Corti. Thus, morphological observations confirmed that a dominant-negative Gjb2 mutation showed incomplete development of the cochlear supporting cells. On the other hand, the development of the sensory hair cells, at least from P5 to P12, was not affected. The present study suggests that Gjb2 is indispensable in the postnatal development of the organ of Corti and normal hearing.
authors.affiliation: Department of Otorhinolaryngology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Inoshita
authors.forename: T
authors.initials: T
authors.lastname: Iizuka
authors.forename: H-O
authors.initials: HO
authors.lastname: Okamura
authors.forename: A
authors.initials: A
authors.lastname: Minekawa
authors.forename: K
authors.initials: K
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Furukawa
authors.forename: T
authors.initials: T
authors.lastname: Kusunoki
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008953:Models, Anatomic; D009154:Mutation / Q000235:genetics*; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D009925:Organ of Corti / Q000254:growth & development* / Q000648:ultrastructure; D011571:Psychoacoustics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D013912:Threonine / Q000235:genetics; D014364:Tryptophan / Q000235:genetics
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D000072259:Connexin 26; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013912:Threonine; D014364:Tryptophan; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3; D009218:Myosins