Distribution and developmentally regulated expression of murine polycystin
Distribution and developmentally regulated expression of murine polycystin
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DOI：
10.1152/ajprenal.1997.272.4.f451
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发表时间：
1997-04-01
影响因子：
4.2
通讯作者：
Zhou, J
中科院分区：
文献类型：
--
作者：
Geng, L;Segal, Y;Zhou, J
PKD 1是在人类中与85%的常染色体显性多囊肾病（ADPKD）病例相似的情况下突变的基因，最近已被鉴定（Eur. PKD财团。Cell 77：881-894，1994;以及，Cell 78：1994中的勘误）。PKD 1的最长的开放阅读框编码多囊蛋白，一种类似于460-kDa蛋白的新蛋白，其含有一系列NH 2-末端粘附结构域（J. Hughes，C. J. Ward，B.佩拉尔河阿斯平沃尔湾Clark，J. San Millan，V. Gamble和P. C。哈里斯Nat. Genet. 10：151-160，1995;和Int. PKD Consortium. Cell 81：289-298，1995）和几个推定的跨膜区段。为了将多囊蛋白的研究扩展到实验动物，我们分离了编码PKD 1的3'端的cDNA克隆，PKD 1的小鼠同源物，并提出了针对重组小鼠多囊蛋白的特异性抗体。该抗体用于通过Western分析和免疫细胞化学确定蛋白质的亚细胞定位和组织分布。在小鼠中，多囊蛋白是一种类似于400 kDa的分子，主要存在于组织和细胞提取物的膜组分中。它在许多组织中表达，包括肾、肝、胰腺、心脏、肠、肺和脑。肾表达，这是局限于肾小管上皮细胞，是最高的胎儿晚期和新生儿早期的生活和出生后第三周下降20倍，保持这一水平到成年。因此，多囊蛋白表达的时间分布与肾小管分化和成熟一致。
PKD1, the gene that is mutated in similar to 85% of autosomal dominant polycystic kidney disease (ADPKD) cases in humans, has recently been identified (Eur. PKD Consortium. Cell 77: 881-894, 1994; also, erratum in Cell 78: 1994). The longest open-reading frame of PKD1 encodes polycystin, a novel similar to 460-kDa protein that contains a series of NH2-terminal adhesive domains (J. Hughes, C. J. Ward, B. Peral, R. Aspinwall, K. Clark, J. San Millan, V. Gamble, and P. C. Harris. Nat. Genet. 10: 151-160, 1995; and Int. PKD Consortium. Cell 81: 289-298, 1995) and several putative transmembrane segments. To extend studies of polycystin to an experimentally accessible animal, we have isolated a cDNA clone encoding the 3' end of Pkd1, the mouse homologue of PKD1, and raised a specific antibody to recombinant murine polycystin. This antibody was used to determine the subcellular localization and tissue distribution of the protein by Western analysis and immunocytochemistry. In the mouse, polycystin is an similar to 400-kDa molecule that is predominantly found in membrane fractions of tissue and cell extracts. It is expressed in many tissues including kidney, liver, pancreas, heart, intestine, lung, and brain. Renal expression, which is confined to tubular epithelia, is highest in late fetal and early neonatal life and drops 20-fold by the third postnatal week, maintaining this level into adulthood. Thus the temporal profile of polycystin expression coincides with kidney tubule differentiation and maturation.