GJB2基因突变约占所有非综合征性遗传性耳聋病例的20-50%。在不同的Cx26-null小鼠模型中观察到Corti(OC)的畸形器官,这主要是由支柱细胞(PC)的发育停滞引起的。然而,由Cx26缺失引起的PC发育异常的机制尚不清楚。在这项研究中,在Cx26-null小鼠中观察到不同出生后天数的PC超微结构。耳蜗Cx26的敲除导致远离中心体而不是靠近中心体的非中心体微管组织中心(MTOC)的畸形组装。此外,异常非中心体MTOC发射的微管(MT)阵列显着减少。此外,我们发现钙调蛋白的表达受到调节,血影蛋白相关蛋白2(camsap2),一种与非中心体MT组织相关的微管负端靶向蛋白,Cx26-null组中的青少年PC减少。我们的结果表明,耳蜗PC中非中心体MTOC的畸形可能导致相应的MTs不能被捕获和锚定在Cx26-null小鼠中,导致OC畸形。此外,这种异常的发育过程可能与早期发育阶段Cx26缺失引起的camsap2表达减少有关。
Mutations in the GJB2 gene account for approximately 20-50% of all non-syndromic hereditary deafness cases. The malformed organ of Corti (OC) was observed in different Cx26-null mouse models, which was mainly caused by the developmental arrest of pillar cells (PCs). However, the mechanism of developmental abnormalities in PCs caused by Cx26 deletion is still unclear. In this study, the ultrastructure of PCs at different postnatal days was observed in Cx26-null mice. Knockout of cochlear Cx26 led to the malformed assembly of non-centrosomal microtubule-organizing centers (MTOCs) far from the centrosome rather than near the centrosome. Additionally, the microtubule (MT) arrays emitted by abnormal non-centrosomal MTOCs were significantly reduced. In addition, we found that the protein expression of calmodulin-regulated, spectrin-associated protein2 (camsap2), a microtubule minus-end targeting protein associated with the organization of non-centrosomal MTs, was decreased in juvenile PCs in the Cx26-null group. Our results indicated that the malformation of non-centrosomal MTOCs in cochlear PCs might lead to the corresponding MTs\' failure to be captured and anchored in Cx26-null mice, which results in the deformity of OC. Additionally, this abnormal developmental process might be correlated with the reduced expression of camsap2 caused by Cx26 deletion in the early developmental stage.