Urinary bladder hypertrophy characteristic of male ROMK Bartter's mice does not occur in female mice

Am J Physiol Regul Integr Comp Physiol. 2018 Mar 1;314(3):R334-R341. doi: 10.1152/ajpregu.00315.2017. Epub 2017 Nov 1.


The renal outer medullary potassium channel (ROMK; Kir1.1) plays an important role in Na+ and K+ homeostasis. ROMK knockout (KO) mice 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 mice. 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 mice. 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 two to approximately fourfold greater than wild-type (WT) mice, but there was no difference in either female or ROMK1 KO mice. The thickness of the urothelium was 648.8 ± 33.2 µm vs. 302.7 ± 16.5 µm ( P < 0.001) and the detrusor muscle 1,940.7 ± 98.9 µm vs. 1,308.2 ± 102.1 µm ( P = 0.013), respectively, in 12-mo male ROMK KO mice 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 quantitative 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.

Keywords: KATP channel; detrusor muscle; gender-sex; kidney; knockout mice; urothelium.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bartter Syndrome / genetics
  • Bartter Syndrome / metabolism*
  • Bartter Syndrome / pathology
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Hydronephrosis / genetics
  • Hydronephrosis / metabolism*
  • Hydronephrosis / pathology
  • Hypertrophy
  • Male
  • Mice, Knockout
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Organ Size
  • Phenotype
  • Potassium Channels, Inwardly Rectifying / deficiency
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Sex Factors
  • Ureter / metabolism
  • Ureter / pathology
  • Urethra / metabolism
  • Urethra / pathology
  • Urinary Bladder / metabolism*
  • Urinary Bladder / pathology
  • Urothelium / metabolism
  • Urothelium / pathology


  • Kcnj1 protein, mouse
  • Potassium Channels, Inwardly Rectifying