title: Female ROMK null mice manifest more severe Bartter II phenotype on renal function and higher PGE2 production.
abstract: 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.
authors.affiliation: Dept. of Cellular and Molecular Physiology, Yale Univ. School of Medicine, 333 Cedar St., New Haven, CT 06520, USA.
authors.forename: Qingshang
authors.initials: Q
authors.lastname: Yan
authors.forename: Xinbo
authors.initials: X
authors.lastname: Yang
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cantone
authors.forename: Gerhard
authors.initials: G
authors.lastname: Giebisch
authors.forename: Steven
authors.initials: S
authors.lastname: Hebert
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D001477:Bartter Syndrome / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology*; D001835:Body Weight; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D006869:Hydronephrosis / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010641:Phenotype; D011188:Potassium / Q000652:urine; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D012727:Sex Characteristics; D012964:Sodium / Q000652:urine; D015996:Survival Rate; D013929:Thromboxane B2 / Q000378:metabolism; D014556:Urine
chemical_list: C510693:Kcnj1 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying; D013929:Thromboxane B2; D012964:Sodium; D015232:Dinoprostone; D011188:Potassium