Morphologic Characterization of Polycystic Kidney in inv Transgenic Mouse

ABSTRACT

The aim of this study was to characterize the morphology of a polycystic kidney which was found in 100% of the transgenic mice homozygous for inv mutation and to gain insight into the pathogenesis of inherited polycystic kidney disease during the pre- and postnatal periods. The fetal and postnatal kidneys from the homozygous and heterozygous transgenic mice were examined by the light, transmission and scanning electron microscopes, image analyzer, and an immunohistochemistry utilizing the antibodies specific for each segment of the renal tubules (Tetragonolobus purpureas, Arachis hypogaea, Tamm-Horsfall protein, AE1/AE3, EMA, vimentin, Phaseolus vulgaris) was performed to determine the site of origin of renal cysts. Two developmental phases of a cystic disease were identified. The first phase, seen in fetal kidneys, was characterized by dilatation mainly of the proximal tubules and a few distal tubules. The later phase, in postnatal period, was characterized by progressive enlargement of the kidneys due to mainly cystic change of the collecting ducts, which distorted the normal architecture of both cortex and medulla and almost completely replaced the renal parenchyma. The cystic dilatation involved all segments of the nephron and the collecting duct as well as the Bowman's spaces of glomeruli. The epithelial cell hyperplasia was found as a micropolyp formation within the renal cysts and an increase in PCNA positive cells. These findings suggest that a cyst is not simply a ballooning of a renal tubule and the stretching of cells, formerly thought to be due to an altered compliance of an abnormal basement membrane, but indeed the result of increased numbers of tubular epithelial cells.