Raphael Kalani L, Strait Kevin A, Stricklett Peter K, Miller R Lance, Nelson Raoul D, Piontek Klaus B, Germino Gregory G, Kohan Donald E
Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
Kidney Int. 2009 Mar;75(6):626-33. doi: 10.1038/ki.2008.659. Epub 2009 Jan 14.
Renal cysts in autosomal dominant polycystic kidney disease arise from cells throughout the nephron, but there is an uncertainty as to whether both the intercalated cells (ICs) and principal cells (PCs) within the collecting duct give rise to cysts. To determine this, we crossed mice containing loxP sites within introns 1 and 4 of the Pkd1 gene with transgenic mice expressing Cre recombinase under control of the aquaporin-2 promoter or the B1 subunit of the proton ATPase promoter, thereby generating PC- or IC-specific knockout of Pkd1, respectively. Mice, that had Pkd1 deleted in the PCs, developed progressive cystic kidney disease evident during the first postnatal week and had an average lifespan of 8.2 weeks. There was no change in the cellular cAMP content or membrane aquaporin-2 expression in their kidneys. Cysts were present in the cortex and outer medulla but were absent in the papilla. Mice in which PKd1 was knocked out in the ICs had a very mild cystic phenotype as late as 13 weeks of age, limited to 1-2 cysts and confined to the outer rim of the kidney cortex. These mice lived to at least 1.5 years of age without evidence of early mortality. Our findings suggest that PCs are more important than ICs for cyst formation in polycystic kidney disease.
常染色体显性多囊肾病中的肾囊肿起源于整个肾单位的细胞，但关于集合管内的闰细胞（ICs）和主细胞（PCs）是否都会产生囊肿仍存在不确定性。为了确定这一点，我们将在Pkd1基因内含子1和4中含有loxP位点的小鼠与在水通道蛋白-2启动子或质子ATP酶启动子的B1亚基控制下表达Cre重组酶的转基因小鼠进行杂交，从而分别产生PC或IC特异性的Pkd1基因敲除小鼠。PCs中Pkd1被敲除的小鼠在出生后第一周就出现了进行性囊性肾病，平均寿命为8.2周。它们肾脏中的细胞cAMP含量或膜水通道蛋白-2表达没有变化。囊肿出现在皮质和外髓质，但乳头中没有。ICs中PKd1被敲除的小鼠直到13周龄时才有非常轻微的囊性表型，仅限于1 - 2个囊肿，且局限于肾皮质的外缘。这些小鼠活到至少1.5岁，没有早期死亡的迹象。我们的研究结果表明，在多囊肾病中，PCs对囊肿形成比ICs更重要。
