Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule
Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule
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DOI：
10.1128/mcb.25.17.7770-7779.2005
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发表时间：
2005-09-01
影响因子：
5.3
通讯作者：
Ishibashi, K
中科院分区：
文献类型：
--
作者：
Morishita, Y;Matsuzaki, T;Ishibashi, K
水通道蛋白-11(Aquaporin-11，AQP11)是由天冬酰胺-脯氨酸-丙氨酸(NPA)盒形成的特殊孔洞蛋白，但其功能尚不清楚。我们调查了它对肾脏的潜在贡献。免疫组织化学显示AQP11定位于近端小管细胞内。将AQP11基因导入CHO-K1细胞后，定位于细胞内细胞器。产生了AQP11缺失的小鼠；这些小鼠表现出近端小管的空泡化和包囊形成。AQP11基因缺失的小鼠出生正常，但在断奶前死亡，原因是晚期肾功能衰竭伴多囊肾，其中囊肿占据了整个皮质。值得注意的是，囊上皮含有空泡。这些空泡存在于新生小鼠的近端小管中。在3周大的小鼠中，这些小管含有多个囊。原代培养的近端小管细胞显示AQP11基因缺失的小鼠体内存在酸化缺陷。这些数据表明，AQP11对近端肾小管功能是必不可少的。AQP11基因缺失的小鼠是一种新的多囊肾病模型，将为囊变的发生提供新的机制。
Aquaporin-11 (AQP11) has been identified with unusual pore-forming NPA (asparagine-proline-alanine) boxes, but its function is unknown. We investigated its potential contribution to the kidney. Immunohistochemistry revealed that AQP11 was localized intracellularly in the proximal tubule. When AQP11 was transfected in CHO-K1 cells, it was localized in intracellular organelles. AQP11-null mice were generated; these mice exhibited vacuolization and cyst formation of the proximal tubule. AQP11-null mice were born normally but died before weaning due to advanced renal failure with polycystic kidneys, in which cysts occupied the whole cortex. Remarkably, cyst epithelia contained vacuoles. These vacuoles were present in the proximal tubules of newborn mice. In 3-week-old mice, these tubules contained multiple cysts. Primary cultured cells of the proximal tubule revealed an endosomal acidification defect in AQP11-null mice. These data demonstrate that AQP11 is essential for the proximal tubular function. AQP11-null mice are a novel model for polycystic kidney diseases and will provide a new mechanism for cystogenesis.