Abstract
A laboratory model of membranous glomerulonephritis was induced in rats by the injection of pronase-digested homologous renal tubular epithelial antigen, and the renal lesions in the experimentallyinduced nephritis were studied sequentially by electron microscope. Rat tubular antigen, which was obtained from pronase-treated tubular segments and partified by gel filtration through a Bio-Gel column, was emulsified in the same volume of Freund's adjuvant and injected in rear foot pads of rats. After the antigen injection, urinary protein was determined quantitatively and the kidneys were obtained by unilateral nephrectomy or sacrifice at the intervals of 1-4 weeks. Proteinuria developed about 6 weeks after the antigen injection. In the renal specimens taken 3 weeks after the antigen injection, a few electron-dense deposits were first detected along subepithelial surface of the GBM. Epithelial foot processes often fused to each other at the place of deposition. After the appearance of proteinuria, the amount of deposits increased in number and size, and the fusion of foot processes became widespread. Small deposits were also found near the epithelial slit membrane. In the more advanced cases, about 3 months after the appearance of proteinuria, the GBM was thickened irregularly, containing many deposits within it, In much more survived rats, the deposits were seen a rough granule. There were some areas of low electron density or electron-lucent areas. These ultrastructural changes observed in the experimental nephritis were similar to those observed in human membranous glomerulonephritis. In some rats, however, which were weakened gradually and dead within 6 months after the development of proteinuria, marked thickening of the GBM with numerous dense deposits were found. No electron-lucent areas in the GBM were observed in these rats.