Nedd4–2 labeling is reduced in ICs taken from cortical collecting ducts of IC Nedd4–2 knockout mice. This slide shows cortical sections from an Nedd4–2 knockout mouse and a wild-type littermate labeled for AQP2 (blue; a principal cell marker) and Nedd4–2 (brown). Asterisks mark AQP2-positive (principal) cells, whereas arrows show AQP2-negative (IC) cells. In cortical sections from wild-type mice, Nedd4–2 label was observed in both ICs and principal cells. However, in the IC Nedd4–2 null mice, whereas Nedd4–2 label was seen in principal cells, Nedd4–2 label was observed in only rare ICs (AQP2-negative cells).