MOLECULAR ANALYSIS OF SPONTANEOUS GLOMERULOSCLEROSIS IN OS + MICE, A MODEL WITH REDUCED NEPHRON MASS/

Oligosyndactyly mice (ROP Os/+) are a radiation-induced mutant strain with reduced glomerular number and increased glomerular size. We found that they develop glomerulosclerosis. At 3 mo, ROP Os/+ mice had diff use mesangial expansion by light microscopy, whereas their +/+ litterm ates did not. Electron microscopic morphometry revealed a twofold incr ease in mesangial areas but no changes in the thickness of glomerular basal laminae. Mean glomerular volume was increased 1.8-fold. Cell num ber and thymidine labeling index were increased 1.3- and 2.4-fold, res pectively. The amount of glomerular type IV collagen and tenascin but not laminin was increased by immunofluorescence microscopy. mRNA level s in microdissected glomeruli were measured by competitive reverse tra nscription-polymerase chain reaction and corrected for cell number. al pha(1)-Chain type IV collagen and tenascin mRNAs were increased 3.2-fo ld and 1.8-fold, whereas laminin B1 mRNA levels were not. The levels o f 72-kDa collagenase rnRNA were increased 1.6-fold. Transforming growt h factor-beta 1 mRNA levels were elevated 1.8 fold, but platelet-deriv ed growth factor-beta 1 mRNA levels remained normal. This is the first analysis of glomerular molecular and cellular changes in a model of c ongenital nephron reduction.