STUDIES OF GLOMERULAR CELLS DERIVED FROM TRANSGENIC MICE

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Glomerulosclerosis, characterized by increased glomerular cell turnover and increased turnover of extracellular matrix turnover, is the leading cause of renal failure in the US. Current studies in humans or animal 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. This is due, in part, to the difficulty in isolating and characterizing glomeruli in vivo, and the fact that, the glomerulus contains three indigenous cell types and a population of bone marrow-derived macrophages. This is particularly a problem with mice, a species we have chosen to study because of the availability of considerable genetic information about extracellular matrix and growth regulatory factors. We have approached this problem by isolating the individual cell types and characterizing them in vitro. The sources of the cells types examined include normal mice, non-obese diabetic mice, and mice transgenic for bovine growth hormone. We first examined the question of the phenotypic modulation of glomerular mesangial cells in vitro, addressing the question of whether this occurred, what was the time frame of the occurrence, and whether there was a difference between mesangial cells from different isolates or different sources. We found that there was a marked difference between cells at different passages, as well as between different isolates, and different mouse strains.