Deafness in occludin-deficient mice with dislocation of tricellulin and progressive apoptosis of the hair cells.
Deafness in occludin-deficient mice with dislocation of tricellulin and progressive apoptosis of the hair cells.
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DOI：
10.1242/bio.20147799
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发表时间：
2014-07-25
期刊：
影响因子：
2.4
通讯作者：
Tsukita S
中科院分区：
文献类型：
--
作者：
Kitajiri S;Katsuno T;Sasaki H;Ito J;Furuse M;Tsukita S
封闭蛋白是第一个在紧密连接（TJ）中鉴定的蛋白质，但其功能在很大程度上仍不清楚。已证明TJ在内耳功能中起重要作用，并且闭合蛋白在内耳的所有上皮TJ中表达。因此，我们检查了闭合蛋白缺陷（Occ−/−）小鼠的内耳。虽然内耳最初在Occ−/−小鼠中正常发育，但出生后第12天左右Corti器官中的毛细胞发生凋亡，并发生耳聋。由于在Occ−/−小鼠的耳蜗外植体培养物中未观察到毛细胞变性，因此认为环境变化是细胞死亡的触发因素。至于前庭系统，Occ−/−小鼠的形态和功能均正常。Occ−/−小鼠的这些表型与claudin-14或claudin-9缺陷小鼠的表型非常相似，这使我们推测存在由TJ异常诱导的失衡，例如局部离子成分。此外，闭合蛋白缺乏导致三纤维素的错位，三纤维素是一种导致人类耳聋的基因DFNB 49。Occ-/-小鼠的耳聋可能是由于三纤维素的这种错位造成的。
Occludin is the first identified protein in the tight junction (TJ), but its function has remained for the most part obscure. TJs have been demonstrated to play important roles in the inner ear function, and occludin is expressed in all the epithelial TJs in the inner ear. Thus, we examined the inner ears of occludin-deficient (Occ−/−) mice. Although inner ears initially developed normally in Occ−/− mice, apoptosis occurs in hair cells in the organ of Corti around day 12 after birth, and deafness develops. Since hair cell degeneration was not observed in cochlear explant cultures of Occ−/− mice, environmental changes were considered to be the trigger of cell death. As for the vestibular system, both the morphologies and functions are normal in Occ−/− mice. These phenotypes of Occ−/− mice are very similar with those of claudin-14 or claudin-9 deficient mice, leading us to speculate on the existence of imbalance induced by TJ abnormalities, such as localized ionic components. Moreover, the occludin deficiency led to dislocalization of tricellulin, a gene responsible for human deafness DFNB49. The deafness in Occ−/− mice may be due to this dislocalization of tricellulin.
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DOI：
10.1083/jcb.200510043
发表时间：
2005-12-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ikenouchi J;Furuse M;Furuse K;Sasaki H;Tsukita S;Tsukita S
通讯作者：
Tsukita S
影响因子：
15.9
作者：
Nayak, Gowri;Lee, Sue I.;Riazuddinl, Saima
通讯作者：
Riazuddinl, Saima
影响因子：
4.8
作者：
Doi, Y;Itoh, M;Tsukita, S
通讯作者：
Tsukita, S
影响因子：
9.8
作者：
Borck, Guntram;Rehman, Atteeq Ur;Kubisch, Christian
通讯作者：
Kubisch, Christian
DOI：
10.1073/pnas.92.21.9815
发表时间：
1995-10-10
影响因子：
11.1
作者：
HASSON, T;HEINTZELMAN, MB;MOOSEKER, MS
通讯作者：
MOOSEKER, MS