Aqp2F204V/F204V mice suffer from severe hydronephrosis (Figure 2A and 2B), presumably as a consequence of an inability to cope with the extreme polyuria. We found distended kidneys in all Aqp2F204V/F204V mice; however, the degree of inflation was variable in affected mice and worsened with age. Severe hydronephrosis has previously been observed in double Aqp1/Aqp3 knock-out mice [17], and appears at 6 wk. Even at 4 wk, Aqp2F204V/F204V mice had hydronephrosis. Histologic sections from Aqp2F204V/F204V mice demonstrated marked dilatation of the renal pelvis yet normal morphology of the ureter (Figure 2C and 2D). In particular, the muscularis propria was neither hypertrophied nor thinned. There was the normal festooned appearance of the urothelium, and this transitional epithelium was of normal thickness. There was thinning of the kidney as measured from renal capsule to renal pelvis. However, the morphologic features of the glomeruli and proximal/distal tubules were unremarkable (Figure 2D).