School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
Hear Res. 2019 Jun;377:247-259. doi: 10.1016/j.heares.2019.04.002. Epub 2019 Apr 8.
Brg1 is an ATPase subunit of the SWI/SNF chromatin-remodeling complex, and it is indispensable for the development and homeostasis of various organs. Conditional deletion of Brg1 in cochlea hair cells (HCs) leads to multiple structural defects and profound deafness. However, the premature death of Brg1-deficient cochlea HCs hindered further study of the role of Brg1. In contrast to cochlea HCs, Brg1-deficient vestibular HCs survived for a long time. Therefore, HC apical structure and vestibular function were examined in inner HC-specific conditional Brg1 knockout mice. Vestibular HCs exhibited fused and elongated stereocilia bundles after deletion of Brg1, and the cuticular plate was absent in most HCs with fused stereocilia bundles. HC loss was observed in conditional Brg1 knockout mice at the age of 12 months. Morphological defects and HC loss were primarily restricted in the striolar region of the utricle and saccule and in the central region of ampulla. The behavioral tests revealed that Brg1 deletion in HCs caused vestibular dysfunction in older adult mice. These results suggest that Brg1 may play specific roles in the maintenance of the HC stereocilia bundle and the cuticular plate.
Brg1 是 SWI/SNF 染色质重塑复合物的 ATP 酶亚基，它对于各种器官的发育和稳态是不可或缺的。条件性敲除耳蜗毛细胞（HCs）中的 Brg1 会导致多种结构缺陷和严重的耳聋。然而，Brg1 缺陷型耳蜗 HCs 的过早死亡阻碍了对 Brg1 作用的进一步研究。与耳蜗 HCs 不同，Brg1 缺陷型前庭 HCs 可以长期存活。因此，在内耳 HCs 特异性条件性 Brg1 敲除小鼠中检查了 HC 顶端结构和前庭功能。Brg1 缺失后，前庭 HCs 的静纤毛束融合且变长，大多数融合静纤毛束的 HC 中没有表皮板。在 12 月龄的条件性 Brg1 敲除小鼠中观察到 HC 丢失。形态缺陷和 HC 丢失主要局限于椭圆囊和球囊的嵴状区以及壶腹的中央区。行为学测试表明，HCs 中的 Brg1 缺失导致老年小鼠前庭功能障碍。这些结果表明，Brg1 可能在维持 HC 静纤毛束和表皮板方面发挥特定作用。
