Current models of glomerulosclerosis (GS) have yielded little information about the cellular and molecular abnormalities that are critical in the initiation and progression of this disease. The complexity of the kidney and glomerulus make isolation and examination of pure cultured populations of glomerular cells an attractive method for beginning to answer these questions. Unfortunately other models of GS involve extrarenal causes of glomerular injury. Because of this it is quite likely that glomerular cells isolated from thse models would not maintain the abnormal behavior in vitro which led to the development of GS in vivo. We have identified several lines of mice transgenic for the early region of simian virus 40 (SV40) that develop progressive glomerulosclerosis. As there are no evident extrarenal sources of injury, and since expression of the foreign DNA has been documented to occur in whole kidney we suspect that the glomerular disease may be secondary to expression of the foreign DNA by glomerular cells in vivo. We have isolated lines of glomerular endothelial, mesangial, and epithelial cells from transgenic mice and have isolated pure cultures of mesangial and epithelial cells from their normal litter mates. As preliminary data from the in vivo model indicates that proliferation of glomerular cells is an early event in the development of GS in transgenic mice we plan to begin the evaluation of several growth factors on the behavior of individual cells.
