Hydronephrosis and Urinary Bladder Hypertrophy in ROMK Bartter's Mouse

The renal outer medullary potassium channel (ROMK; K ir 1.1) plays an important role in Na + and K + homeostasis. ROMK knockout mice (KO) show a similar phenotype to Bartter's syndrome of salt wasting and dehydration due to reduced Na‐2Cl‐K‐cotransporter activity. ROMK KO mice also show hydronephrosis; however, the mechanism of this phenotype has not been understood. We investigated ROMK expression and regulation by high and low K intake in mouse bladder, by Western blot and immunofluorescence (IF) staining. We also compared the bladder weight, bladder capacity, and thickness of urothelium and smooth muscle layer between WT and ROMK KO mice. Western blotting detected ROMK expression at 45~48 kDA, and IF staining showed that the luminal membrane of umbrella cells were strongly stained in WT compared to KO mice. The expression of ROMK in the luminal membrane disappeared and signal intensity of the detrusor muscle was decreased by low potassium diet (LK) in WT mice. In contrast, there was no significant change in ROMK intensity, but the thickness of urothelium was increased after mice were treated with HK diet. The thickness of urothelium was 168.1±25.8 μ m in normal K (NK) and was 300.7±83.6 μ m (p<0.001) in the HK treated group compared with NK in WT mice at the same age. The bladder weight, bladder capacity and the thickness of urothelium in ROMK KO showed average increases 2~4 fold greater than WT at both 2 months and 12 months of age. The thickness of the urothelium was 648.8±33.2 μ m vs 302.7±16.5 μ m (p<0.001) and the detrusor muscle 1940.7±98.9 μ m vs 1308.2±102.1 μ m (p=0.013) respectively in 12‐month ROMK KO mice. In conclusion, ROMK expressed in the urinary bladder can be regulated by K + intake; significant enlargement and hypertrophy of the bladder may contribute to hydronephrosis in ROMK KO mice. Support or Funding Information NIH RO1 DK099284 and PO1 DK 17433