Female ROMK null mice manifest more severe Bartter II phenotype on renal function and higher PGE2 production

Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut Submitted 24 January 2007 ; accepted in final form 21 June 2008 ROMK null mice with a high survival rate and varying severity of hydronephrosis provide a good model to study type II Bartter syndrome pathophysiology (26). During the development of such a colony, we found that more male than female null mice survived, 58.7% vs. 33.3%. To investigate the possible mechanism of this difference, we compared the survival rates, renal functions, degree of hydronephrosis, as well as PGE 2 and TXB 2 production between male and female ROMK wild-type and null mice. We observed that female ROMK Bartter's mice exhibited lower GFR (0.37 vs. 0.54 ml·min –1 ·100 g BW –1 , P < 0.05) and higher fractional Na + excretion (0.66% vs. 0.48%, P < 0.05) than male Bartter's. No significant differences in acid-base parameters, urinary K + excretion, and plasma electrolyte concentrations were observed between sexes. In addition, we assessed the liquid retention rate in the kidney to evaluate the extent of hydronephrosis and observed that 67% of male and 90% of female ROMK null mice were hydronephrotic mice. Urinary PGE 2 excretion was higher in both sexes of ROMK null mice: 1.35 vs. 1.10 ng/24 h in males and 2.90 vs. 0.87 ng/24 h in females. TXB 2 excretion was higher in female mice in both wild-type and ROMK null mice. The increments of urinary PGE 2 and TXB 2 were significantly higher in female null mice than males, 233.33% vs. 22.74% of PGE 2 and 85.67% vs. 20.36% of TXB 2 . These data demonstrate a more severe Bartter phenotype in female ROMK null mice, and higher PGE 2 and TXB 2 production may be one of the mechanisms of this manifestation. gender difference; ROMK Bartter's; hydronephrosis; renal function Address for reprint requests and other correspondence: T. Wang, Dept. of Cellular and Molecular Physiology, Yale Univ. School of Medicine, 333 Cedar St., New Haven, CT 06520 (e-mail: tong.wang{at}yale.edu )