Figure 5.

Treatment of Alport mice with MMI270 arrests progressive loss of glomerular structure and function. Treatment with MMI270 from 3 to 7 weeks of age results in markedly improved glomerular basement membrane architecture. Representative glomerular capillary loops are shown from a 7-week-old: A: Wild-type mouse; B: Alport mouse; C: Alport mouse treated from 4 to 7 weeks with MMI270. Scale bar = 1 μm. Immunogold localization of type IV collagen revealed evidence for focal degradation in thickened regions of the GBM. Immunogold localization of type IV collagen was used to examine the integrity of the collagen network in the GBM in Alport mice. D: a sparse subendothelial labeling pattern in the GBM of a wild-type mouse. In Alport mice, areas of the capillary loop that were structurally normal displayed a regular distribution of gold particles along the lamina densa (E). Areas where focal thickening of the GBM was observed showed evidence of focal degradation of the collagen network (F). Arrows denote evidence of a collagen network splitting, where gold deposition is primarily on the epithelial or endothelial aspect of the GBM. There was no significant variation in gold particles per unit length of the GBM in Alport mice, suggesting that collagen is not accumulating in the thickened regions. Scale bar = 50 nm.