Urinary Bladder Hypertrophy is Susceptible in Male but Protected in Female ROMK Bartter's Mouse

The renal outer medullary potassium channel (ROMK; K_ir1.1) 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 but not in ROMK1 KO. ROMK KO mice also show hydronephrosis; however, the mechanism of this phenotype has not been understood. We have previously demonstrated a gender-sex difference in hydronephrosis and PGE2 production in ROMK KO mouse. In this study we compared the gender-sex difference in bladder hypertrophy and hydronephrosis in ROMK KO mice. The bladder weight, bladder capacity and the thickness of urothelium in male ROMK KO showed average increased 2~4 fold greater than WT but there was no difference in either female or ROMK1 KO. The thickness of the urothelium was 648.8±33.2 vs. 302.7±16.5 (p<0.001) and the detrusor muscle 1940.7±98.9 vs. 1308.2±102.1 (p=0.013) respectively in 12-month males ROMK KO compared with the same-age WT mice. Western blotting detected ROMK expression at 45~48 kDa, and both ROMK1 and ROMK2 mRNA were detected by Q-PCR in the bladder. Immunofluorescence staining showed ROMK stained in the bladder, ureter and urethra in WT but not in KO. In addition, there was a correlation between the severity of hydronephrosis and the bladder weight in male but not in female ROMK KO mice. In conclusion, ROMK expressed in the urinary tract at both protein and mRNA levels; significant enlargement and hypertrophy of the bladder may contribute to hydronephrosis in male ROMK KO mice.

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