title: Dominant negative connexin26 mutation R75W causing severe hearing loss influences normal programmed cell death in postnatal organ of Corti.
abstract: BACKGROUND
  The greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti. Situated near the inner hair cells of neonatal mice, the GER undergoes a wave of apoptosis after postnatal day 8 (P8). We evaluated the GER from P8 to P12 in transgenic mice that carry the R75W + mutation, a dominant-negative mutation of human gap junction protein, beta 2, 26 kDa (GJB2) (also known as connexin 26 or CX26). Cx26 facilitate intercellular communication within the mammalian auditory organ.
  
  
  RESULTS
  In both non-transgenic (non-Tg) and R75W + mice, some GER cells exhibited apoptotic characteristics at P8. In the GER of non-Tg mice, both the total number of cells and the number of apoptotic cells decreased from P8 to P12. In contrast, apoptotic cells were still clearly evident in the GER of R75W + mice at P12. In R75W + mice, therefore, apoptosis in the GER persisted until a later stage of cochlear development. In addition, the GER of R75W + mice exhibited morphological signs of retention, which may have resulted from diminished levels of apoptosis and/or promotion of cell proliferation during embryogenesis and early postnatal stages of development.
  
  
  CONCLUSIONS
  Here we demonstrate that Cx26 dysfunction is associated with delayed apoptosis of GER cells and GER retention. This is the first demonstration that Cx26 may regulate cell proliferation and apoptosis during development of the cochlea.
authors.forename: Ayako
authors.initials: A
authors.lastname: Inoshita
authors.forename: Keiko
authors.initials: K
authors.lastname: Karasawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakubo
authors.forename: Asuka
authors.initials: A
authors.lastname: Miwa
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8431, Japan. kkamiya@juntendo.ac.
authors.forename: Kazusaku
authors.initials: K
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009925:Organ of Corti / Q000166:cytology* / Q000503:physiopathology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26; C505409:Casp3 protein, mouse; D053148:Caspase 3