Sixteen-week-old Pod-Cre fVHL mice have thickened GBM. A: GBM of a 16-week-old wild-type littermate control shows regular podocyte foot process registration adjacent to the entire length of capillary loop GBM. B: 16-week-old mildly proteinuric Pod-Cre fVHL mouse GBM showing overall thickening of the GBM, along with subepithelial “humps” and subendothelial projections. C: Using the orthoganol intercept method, GBM width averaged 291 nm in 16-week-old nonproteinuric Pod-Cre fVHL kidneys, which was almost 100 nm wider than wild-type littermate controls (*P < 0.05). D and E: Glomeruli were isolated from six-week-old nonproteinuric Pod-Cre fVHL mice and littermate controls. Levels of collagen IV (D) and laminin (E) mRNAs were determined by real-time quantitative RT-PCR, and were expressed as ratios (Pod-Cre fVHL/wild-type). Significant increases were seen in Col4a1, Col4a2, and Col4a5, as well as Lamb1 and Lama5 (*P < 0.05).