Division of Cell Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
J Clin Invest. 2013 Sep;123(9):3712-5. doi: 10.1172/JCI69651. Epub 2013 Aug 27.
Tricellulin is a tricellular tight junction-associated membrane protein that controls movement of solutes at these specialized cell intersections. Mutations in the gene encoding tricellulin, TRIC, lead to nonsyndromic deafness. In this issue of the JCI, Nayak et al. created a gene-targeted knockin mouse in order to mimic the pathology of a human TRIC mutation. Deafness appears to be caused either by an increase in the K+ ion concentration around the basolateral surfaces of the outer hair cells or, alternatively, by an increase in small molecules such as ATP around the hair bundle, leading to cellular dysfunction and degeneration. Furthermore, the mice have features suggestive of syndromic hearing loss, which may have implications for care and treatment of patients harboring TRIC mutations.
三细胞紧密连接相关膜蛋白 (tricellulin) 是一种控制这些特化细胞连接处溶质运动的蛋白。编码 tricellulin 的基因(TRIC)发生突变会导致非综合征性耳聋。在本期 JCI 中,Nayak 等人构建了一种基因靶向敲入小鼠,以模拟人类 TRIC 突变的病理。耳聋似乎是由外毛细胞基底外侧表面周围的 K+ 离子浓度增加引起的,或者是由毛束周围的小分子(如 ATP)增加引起的,导致细胞功能障碍和退化。此外,这些小鼠还具有提示综合征性听力损失的特征,这可能对携带 TRIC 突变的患者的护理和治疗具有重要意义。