Gattone V H, Calvet J P, Cowley B D, Evan A P, Shaver T S, Helmstadter K, Grantham J J
Department of Anatomy, University of Kansas Medical Center, Kansas City.
Lab Invest. 1988 Aug;59(2):231-8.
The C57BL/6J-cpk genetic murine model of autosomal recessive polycystic kidney disease was examined to gain insight into the pathogenesis of renal cystic disease. Fetal through 3-week-old offspring of heterozygote matings were used to study growth parameters and morphology of this genetic form of cystic disease. The kidneys were examined by light and electron microscopy and nephron segments were microdissected. Two phases of cystic disease development were morphologically identified. The first phase in fetal and newborn affected pups was characterized by proximal tubule enlargement and a general increase in the tubular mitotic index. The proximal tubules showed cytologic abnormalities along with an increased necrotic cell index. The later phase, in one through 3-week-old cystic pups, was characterized by progressive enlargement of the kidneys due mainly to cystic change of the collecting ducts and by development of azotemia. Secondary to the azotemia was a stunted body growth. Significant tubular epithelial hyperplasia was not found by mitotic index during the second phase, but an increase in collecting duct cellularity was present. Histone H4 gene expression, which is tightly coupled to DNA synthesis and thus an index of cell proliferation, showed only a minimal increase in cystic kidneys at 1, 2, and 3 weeks of age. Therefore, the degree of cell proliferation necessary to allow the observed tubular enlargement appears to be minimal.
对常染色体隐性多囊肾病的C57BL/6J-cpk基因小鼠模型进行了研究，以深入了解肾囊性疾病的发病机制。利用杂合子交配产生的胎儿至3周龄后代，研究这种遗传性囊性疾病的生长参数和形态。通过光镜和电镜检查肾脏，并对肾单位节段进行显微切割。从形态学上确定了囊性疾病发展的两个阶段。胎儿和新生患病幼崽的第一阶段特征为近端小管增大和小管有丝分裂指数普遍增加。近端小管显示出细胞学异常以及坏死细胞指数增加。后期阶段，即1至3周龄的囊性幼崽，特征为肾脏主要由于集合管的囊性改变而逐渐增大，并出现氮质血症。氮质血症继发身体生长发育迟缓。在第二阶段，通过有丝分裂指数未发现明显的肾小管上皮增生，但集合管细胞增多。组蛋白H4基因表达与DNA合成紧密相关，因此是细胞增殖的指标，在1、2和3周龄的囊性肾脏中仅显示出最小程度的增加。因此，使观察到的肾小管增大所需的细胞增殖程度似乎很小。
