Origin of endocochlear potential studied with mouse model for human heredetary nonsyndromic deafness.

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The endocochlear potential (EP) is remarkable electrostatic potential observed between lymph of cochlear duct and that of neighboring duct scala tympani in inner ear. This electro-physiological character is known as specific for higher vertebrate especially in mammalian species and to be essential for their cochlear function. About the origin, the process of establishment, and ways of maintenance of EP, however, are still little known.Recently, Gap junction component connexin 26 (Cx26) is thought to have pivotal role in maintenance of EP as well as transcription factor Brn-4 does. Cx26 is also known as responsive gene for human nonsyndromic deafness DFNB1 and DFNA3. To better understand the mechanism of emergence of EP and to investigate the roles of Cx26 in conjunction with Brn-4, we introduced conditional gene targeting technology using cre-lfcxP system to produce "Cx26-conditional-KO" mice with "silent" alleles of Cx26 those were assumed to work normally in vivo and then induced deletion of Cx26 gene in spatio-temporally dependent manner.By crossing Cx26-conditional-KO mice with PO-Cre transgenic mice, we attempted to eliminate Cx26 gene from whole inner ear tissue cells in their offspring mice of adult age. Auditory brainstem response measurement showed that Cx26-Silent-Allele : O/P0-Cre+ mice were profound deafness whereas Cx26-Silent-Allele:E/PO-Cre+ mice were normal. These results indicate that, like in the case of human nonsyndromic deafness, Cx26 gene is essential for mouse inner ear function and suggest Cx26-Silent-Allele:E/PO-Cre+ mouse could be a model for human DFNB1.