Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease
Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease
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DOI：
10.1172/jc1200214099
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发表时间：
2002-02-01
影响因子：
15.9
通讯作者：
Guay-Woodford, LM
中科院分区：
文献类型：
--
作者：
Hou, XY;Mrug, M;Guay-Woodford, LM
先天性多囊肾（cpk）突变是最广泛表征的多囊肾病（PKD）小鼠模型。肾囊性疾病在纯合子中完全表达，与人类常染色体隐性 PKD (ARPKD) 惊人相似，而遗传背景调节发育中胆管树中相应缺陷的外显率。我们现在描述了 cpk 小鼠中被破坏的新基因的位置克隆、突变分析和表达。 cpk 基因主要在肾脏和肝脏中表达，编码一种亲水性 145 个氨基酸的蛋白质，我们称之为胱氨酸。当在极化的肾上皮细胞中外源表达时，在纤毛中检测到胱氨酸，并且其表达与另一种 PKD 相关蛋白 Polaris 重叠。因此，我们认为单个上皮纤毛在极化上皮的功能分化中很重要，并且纤毛功能障碍是 cpk 小鼠 PKD 表型的基础。
The congenital polycystic kidney (cpk) mutation is the most extensively characterized mouse model of polycystic kidney disease (PKD). The renal cystic disease is fully expressed in homozygotes and is strikingly similar to human autosomal recessive PKD (ARPKD), whereas genetic background modulates the penetrance of the corresponding defect in the developing biliary tree. We now describe the positional cloning, mutation analysis, and expression of a novel gene that is disrupted in cpk mice. The cpk gene is expressed primarily in the kidney and liver and encodes a hydrophilic, 145-amino acid protein, which we term cystin. When expressed exogenously in polarized renal epithelial cells, cystin is detected in cilia, and its expression overlaps with polaris, another PKD-related protein. We therefore propose that the single epithelial cilium is important in the functional differentiation of polarized epithelia and that ciliary dysfunction underlies the PKD phenotype in cpk mice.