[The experimental study on endoplasmic reticulum stress-participated outer hair cell apoptosis in cadherin 23 gene mutant mice].

To test the mechanism and upstream pathway of outer hair cell apoptosis in Cadherin 23 (Cdh23) gene mutant mice. The mutant 23() 57/6 (6) . 70 . - () . () () . -- () / () . . . 23 . The ABR thresholds in mice were significantly higher than those in B6 mice at the age of 1 and 3 months (both <0.05). The surface preparation with TUNEL staining confirmed OHC apoptosis in mouse cochleae which showed a higher TUNEL positive cell ratio than B6 mouse(=11.291, <0.01). The ER stress marker and mRNA were upregulated in the mouse inner ear, when compared with those in the B6 mouse(both <0.05). The BiP protein extracted from the mouse cochleae was significantly higher than that of B6 mouse measured by Western blot (=3.66, =0.02). Immunostaining showed that BiP and CHOP were highly detected in the OHC in mouse cochleae, and was mainly detected in the perinuclear region of OHC. However, a bare BiP and CHOP signal were shown in B6 mouse cochleae. The CDH23 protein was specifically localized at the top of the OHC in B6 mice, indicating the localization of the tip links in hair bundle stereocilia. On the contrary, the CDH23 protein was found to be localized from the top to the nuclei of the OHC in mice. Portions of the CDH23 proteins failed to reach the top of the hair bundles and remained in the OHC cytoplasm. As the downstream response of the Cdh23 gene mutation, portions of the mutant CDH23 protein was accumulated in ER lumen resulting in the increase of ER loading and ultimately triggered ER stress and hair cell apoptosis in mouse cochleae.