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

First Author  Kim JM Year  2018
Journal  Am J Physiol Regul Integr Comp Physiol Volume  314
Issue  3 Pages  R334-R341
PubMed ID  29092859 Mgi Jnum  J:258443
Mgi Id  MGI:6120107 Doi  10.1152/ajpregu.00315.2017
Citation  Kim JM, et al. (2018) Urinary bladder hypertrophy characteristic of male ROMK Bartter's mice does not occur in female mice. Am J Physiol Regul Integr Comp Physiol 314(3):R334-R341
abstractText  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 microm vs. 302.7 +/- 16.5 microm ( P < 0.001) and the detrusor muscle 1,940.7 +/- 98.9 microm vs. 1,308.2 +/- 102.1 microm ( 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.
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