p66Shc^−/− mice develop glomerulonephritis. Immunofluorescence, periodic acid-Schiff (PAS) staining, electronic microscopy of kidney from 12-month-old control (+/+) or p66Shc^−/− (−/−) mice. (A) Ig analysis by fluorescence staining with FITC-conjugated anti–mouse IgG reveals immune complexes diffusely deposited in the glomeruli of kidneys from p66Shc^−/− mice not observed in controls. Scale bar represents 100 μm (n ≥ 7). (B) Histology of PAS-stained kidney sections shows normocellular glomerulus in wild-type mice and diffuse increase in thickening of glomerular basal membrane in p66Shc^−/− mice (400×, n ≥ 3). (C) Ultrastructural analysis of uranyl acetate–stained frozen kidney sections by transmission electron microscopy shows thickening of glomerular basement membranes (BM) in p66Shc^−/− mice versus controls. The external face of the basement membranes of p66Shc^−/− glomeruli appears coarse and irregular, with a clear effacement of foot processes (FPs). Electron dense patches within the thickness of the basement membranes represent immune complex deposits (↘). Scale bar represents 2 μm (n ≥ 14).