Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome
Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome
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DOI：
10.1007/s10162-002-3052-4
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发表时间：
2003-09-01
影响因子：
2.4
通讯作者：
Green, ED
中科院分区：
文献类型：
--
作者：
Royaux, IE;Belyantseva, IA;Green, ED
对小鼠耳蜗和前庭终末器官进行免疫定位研究，以研究内耳中 Pendrin（由 Pendred 综合征基因 (PDS) 编码的蛋白质）的表达模式。该蛋白质仅限于由特殊上皮细胞组成的区域，这些细胞被认为在调节内淋巴的组成和吸收中发挥着关键作用。在耳蜗中，pendrin 在螺旋突起和外沟细胞（及其根突）的细胞顶膜中含量丰富。在前庭终末器官中，壶腹嵴、椭圆囊和球囊的移行细胞以及内淋巴囊细胞的顶膜中发现了 pendrin。发现 Pds 敲除 (Pds(-/-)) 小鼠在所有这些位置均缺乏 pendrin 免疫反应性。组织学研究表明，Pds(-/-)小鼠的血管纹厚度仅为野生型小鼠的三分之二，纹状边缘细胞形状和大小不规则。还进行了功能研究来检查 pendrin 在内淋巴稳态中的作用。使用放置在耳蜗和椭圆囊中的双管电极，测量野生型和 Pds(-/-) 小鼠的耳蜗内电位和内淋巴钾浓度。与纹状体形态的改变一致，Pds(-/-)小鼠的耳蜗电位接近于零并且在缺氧期间没有变化。另一方面，Pds(-/-)小鼠的耳蜗和椭圆囊内淋巴钾浓度接近正常。总之，这些结果表明，pendrin 在血管纹基底和/或中间细胞维持蜗蜗电位的功能中发挥关键作用，但在边缘细胞的钾分泌功能中不起关键作用。
Immunolocalization studies of mouse cochlea and vestibular end-organ were performed to study the expression pattern of pendrin, the protein encoded by the Pendred syndrome gene (PDS), in the inner ear. The protein was restricted to the areas composed of specialized epithelial cells thought to play a key role in regulating the composition and resorption of endolymph. In the cochlea, pendrin was abundant in the apical membrane of cells in the spiral prominence and outer sulcus cells (along with their root processes). In the vestibular end-organ, pendrin was found in the transitional cells of the cristae ampullaris, utriculi, and sacculi as well as in the apical membrane of cells in the endolymphatic sac. Pds-knockout (Pds(-/-)) mice were found to lack pendrin immunoreactivity in all of these locations. Histological studies revealed that the stria vascularis in Pds(-/-) mice was only two-thirds the thickness seen in wildtype mice, with the strial marginal cells showing irregular shapes and sizes. Functional studies were also performed to examine the role of pendrin in endolymph homeostasis. Using double-barreled electrodes placed in both the cochlea and the utricle, the endocochlear potential and endolymph potassium concentration were measured in wild-type and Pds(-/-) mice. Consistent with the altered strial morphology, the endocochlear potential in Pds(-/-) mice was near zero and did not change during anoxia. On the other hand, the endolymphatic potassium concentration in Pds(-/-) mice was near normal in the cochlea and utricle. Together, these results suggest that pendrin serves a key role in the functioning of the basal and/or intermediate cells of the stria vascularis to maintain the enclocochlear potential, but not in the potassium secretory function of the marginal cells.