Submitted on January 24, 2007
Accepted on June 21, 2008
FEMALE ROMK NULL MICE MANIFEST MORE SEVERE BARTTER II PHENOTYPE ON RENAL FUNCTION AND HIGHER PGE2 PRODUCTION
Qingshang Yan1, Xinbo Yang1, Alessandra Cantone1, Gerhard Giebisch2, Steven C. Hebert1, and Tong Wang1*
1 Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States
2 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, United States
* To whom correspondence should be addressed. E-mail: tong.wang{at}yale.edu.
ROMK knockout 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, 58.70% vs. 33.33%. To investigate the possible mechanism of this difference, we compared the survival rates, renal functions, degree of hydronephrosis, PGE2 and TXB2 production between male and female ROMK wild-type and null mice. We observed that female ROMK Bartters mice exhibited lower GFR (0.37 vs. 0.54 ml/min/100gBW, P <0.05) and higher fractional Na+ excretion (0.66% vs. 0.48%, P<0.05) than male Bartters. No significant differences in acid-base parameters, urinary K+ excretion and plasma electrolyte concentrations were observed between genders. 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 PGE2 excretion was higher in both genders of ROMK null mice: 1.35 vs. 1.10 ng/24hr in males and 2.90 vs. 0.87 ng/24hr in females. TXB2 excretion was higher in female mice in both wild-type and ROMK null mice. The increments of urinary PGE2 and TXB2 were significantly higher in female null mice than males, 233.33% vs. 22.74% of PGE2 and 85.67% vs. 20.36% of TXB2. These data demonstrate a more severe Bartter phenotype in female ROMK null mice, and higher PGE2 and TXB2 production may be one of the mechanisms of this manifestation.
