Research Project
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Mutations in the connexin26 gene (GJB2) are the most common genetic cause of congenital bilateral non-syndromic sensorineural hearing loss. Transgenic mice were established carrying human Cx26 with the R75W mutation that was identified in a deaf family with autosomal dominant negative inheritance [Kudo T et al. (2003) Hum Mol Genet 12:995-1004]. A dominant-negative Gjb2 R75W transgenic mouse model shows incomplete development of the cochlear supporting cells, resulting in profound deafness from birth [Inoshita A et al. (2008) Neuroscience 156:1039-1047]. The Cx26 defect in the Gjb2 R75W transgenic mouse is restricted to the supporting cells ; it is unclear why the auditory response is severely disturbed in spite of the presence of outer hair cells (OHCs). The present study was designed to evaluate developmental changes in the in vivo and in vitro function of the OHC, and the fine structure of the OHC and adjacent supporting cells in the R75W transgenic mouse. No detectable distortion product otoacoustic emissions were observed at any frequencies in R75W transgenic mice throughout development. A characteristic phenotype observed in these mice was the absence of the tunnel of Corti, Nuel's space, and spaces surrounding the OHC ; the OHC were compressed and squeezed by the surrounding supporting cells. On the other hand, the OHC developed normally. Structural features of the lateral wall, such as the membrane-bound subsurface cisterna beneath the plasma membrane, were intact. Prestin, the voltage-dependent motor protein, was observed by immunohistochemistry in the OHC basolateral membranes of both transgenic and non-transgenic mice. No significant differences in electromotility of isolated OHCs during development was observed between transgenic and control mice. The present study indicates that normal development of the supporting cells is indispensable for proper cellular function of the OHC.
All 2011 2010 2009 Other
All Journal Article (10 results) (of which Peer Reviewed: 6 results) Presentation (1 results) Remarks (1 results)
Auris Nasus Larynx (Epub ahead of print)
Pages: 1312-1319
Auris Nasus Larynx
Volume: (Epub ahead of print)
Ann Otol Rhinol Laryngol 119(11)
Pages: 576-581
Ann Otol Rhinol Laryngol
Volume: 119(11) Pages: 749-54
Indian J Otolaryngol Head Neck Surg 61
Pages: 193-196
耳鼻咽喉科臨床(0032-6313) 補冊124
Pages: 113-113
Pages: 80-80
Pages: 78-78
Int J Audiol 48(8)
Pages: 576-81
Neuroscience 164
