Electron microscope images of adult wild-type (A and B) and deficient in protective protein cathepsin A mice perfused with lanthanum nitrate. In A, lanthanum nitrate percolates through the intercellular spaces (arrowheads) between adjacent principal cells up to the apical tight junctions. In B, lanthanum nitrate permeates the entire intercellular space (arrowheads) including the apical junctional complexes (arrows) indicating a loss of tight junctions. Lanthanum nitrate is also evident in the epididymal lumen (circles, inset of B). In C, paraffin sections of wild-type mice were immunostained for Cldn3. Cldn3 is located in the apical region of the epithelium (arrow). In cathepsin A-knockout mice, the localization of Cldn3 is cytoplasmic. Furthermore, the interstitial area contains numerous macrophages and large vacuoles are present in the epithelium. Reproduced from Figures 1 and 3 of Hermo et al.9