Genetic interaction of Pkhd1, Pkd1 and Sec63. (a–c) Histological kidney sections (a,c) and aggregate structural and functional data (b) from mice with the indicated genotypes at P21. The Pkhd1del4/del4 background results in increased severity of polycystic disease in Sec63 mutant kidneys. PC1 overexpression rescues the worsened Sec63flox/flox; Ksp-Cre; Pkhd1del4/del4 phenotype to a level that is milder than Sec63flox/flox; Ksp-Cre alone (a–c), although microscopic cysts persist (c). Genotypes in the histograms (b) are indicated by the colors in a; n (from left to right) = 5, 6, 8, 6, 6. Results are mean ± s.e.m.; ANOVA; ***P < 0.001. (d) Immunocytochemical analysis of Sec63 mutant kidneys at P21 showing the increased size of collecting duct cysts (green) resulting from the Pkhddel4/del4 background. Thick ascending limb cysts (red) are unchanged. Scale bars, 2 mm (a); 500 μm (c); 50 μm (d).