Functional Studies Reveal New Mechanisms for Deafness Caused by Connexin Mutations

被引:8
作者
Chang, Qing [1 ]
Tang, Wenxue [1 ]
Ahmad, Shoeb [1 ]
Stong, Benjamin [1 ]
Leu, Grace [1 ]
Lin, Xi [1 ,2 ]
机构
[1] Emory Univ, Sch Med, Dept Otolaryngol, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA
关键词
Biochemical coupling; Cochlea; Connexin; Gap junction; Genetic deafness; HEARING IMPAIRMENT; GAP-JUNCTIONS; INNER-EAR; COCHLEA; FORM; GLUCOSE; MICE;
D O I
10.1097/MAO.0b013e318194f774
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Connexin26 (Cx26) and Cx30 are the major protein subunits forming gap junction (GJ) intercellular channels in the cochlea. Mutations in these 2 Cxs are the major cause of non-syndromic early childhood deafness in humans. The underlying mechanism for cochlear abnormality is unclear. Here, we used targeted Cx30 gene deletion (Cx30(-/-)) mice to investigate molecular mechanisms responsible for Cx mutation-linked deafness. Our hypothesis is that specific loss of GJ-mediated biochemical coupling in the cochlea is sufficient to cause deafness. Study Design: We compared: (1) expression of major cochlear GJ protein subunits, Cx26 and Cx30; and (2) biochemical coupling among cochlear supporting cells in the cochleae of wild type and Cx30(-/-) mice. Methods: Immunolabeling was used to examine the expression of the remaining Cx protein expression in the cochlea of Cx30(-/-) mice. We also used a fluorescent dye diffusion assay performed on a novel flattened cochlear preparation to examine GJ-mediated metabolite transfer among cochlear supporting cells. Results: Estimation of the residual ionic conductance indicated that considerable intercellular ionic coupling remained in the cochlea of Cx30(-/-) mice. Direct measurement of GJ-mediated biochemical coupling showed that the transfer of metabolites among cochlear supporting cells in Cx30(-/-) mice was severely reduced. Conclusion: Our data support that deficiency in GJ-mediated biochemical coupling is sufficient to cause Cx mutation-linked deafness.
引用
收藏
页码:237 / 240
页数:4
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