Alport renal disease pathogenesis is characterized by a progressive irregular thickening, thinning, and splitting of the glomerular basement membrane (GBM), which culminates in a focal and segmental glomerulonephritis and progressive loss of glomerular filtration, leading to uremia and death. A mouse model for this disease was produced using a gene targeting approach (Cosgrove et al., 1996). The resulting model displays renal pathology that is very similar to that observed in humans. As matrix accumulation has long been associated with the thickened regions of the GBM, this model provided a means to study the molecular composition and ultrastructural localization of matrix in these rarefied regions of the GBM in the Alport mouse.

We examined three matrix molecules based on preliminary data; type IV collagen α l and α2 chains, laminin-1 and fibronectin. Immunohistochemical analysis showed that while all three of these molecules localize primarily to the mesangial matrix of normal mouse glomeruli, in the Alport glomeruli these molecules seem to be heavily deposited in the GBM.