Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome

John N. Lorenz, Nancy R. Baird, Louise M. Judd, William T. Noonan, Anastasia Andringa, Thomas C Doetschman, Patrice A. Manning, Lynne H. Liu, Marian L. Miller, Gary E. Shull

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

ROMK is an apical K+ channel expressed in the thick ascending limb of Henle (TALH) and throughout the distal nephron of the kidney. Null mutations in the ROMK gene cause type II Bartter's syndrome, in which abnormalities of electrolyte, acid-base, and fluid-volume homeostasis occur because of defective NaC1 reabsorption in the TALH. To understand better the pathogenesis of type II Bartter's syndrome, we developed a mouse lacking ROMK and examined its phenotype. Young null mutants had hydronephrosis, were severely dehydrated, and -95% died before 3 weeks of age. ROMK-deficient mice that survived beyond weaning grew to adulthood; however, they had metabolic acidosis, elevated blood concentrations of Na+ and CI-, reduced blood pressure, polydipsia, polyuria, and poor urinary concentrating ability. Whole kidney glomerular filtration rate was sharply reduced, apparently as a result of hydronephrosis, and fractional excretion of electrolytes was elevated. Micropuncture analysis revealed that the single nephron glomerular filtration rate was relatively normal, absorption of NaC1 in the TALH was reduced but not eliminated, and tubuloglomerular feedback was severely impaired. These data show that the loss of ROMK in the mouse causes perturbations of electrolyte, acid-base, and fluid-volume homeostasis, reduced absorption of NaCI in the TALH, and impaired tubuloglomerular feedback.

Original languageEnglish (US)
Pages (from-to)37871-37880
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number40
DOIs
StatePublished - Oct 4 2002
Externally publishedYes

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Bartter Syndrome
Potassium Channels
Electrolytes
Extremities
Hydronephrosis
Nephrons
Glomerular Filtration Rate
Feedback
Acids
Homeostasis
Fluids
Blood pressure
Polydipsia
Kidney
Polyuria
Blood
Genes
Acidosis
Weaning
Punctures

ASJC Scopus subject areas

  • Biochemistry

Cite this

Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome. / Lorenz, John N.; Baird, Nancy R.; Judd, Louise M.; Noonan, William T.; Andringa, Anastasia; Doetschman, Thomas C; Manning, Patrice A.; Liu, Lynne H.; Miller, Marian L.; Shull, Gary E.

In: Journal of Biological Chemistry, Vol. 277, No. 40, 04.10.2002, p. 37871-37880.

Research output: Contribution to journalArticle

Lorenz, JN, Baird, NR, Judd, LM, Noonan, WT, Andringa, A, Doetschman, TC, Manning, PA, Liu, LH, Miller, ML & Shull, GE 2002, 'Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome', Journal of Biological Chemistry, vol. 277, no. 40, pp. 37871-37880. https://doi.org/10.1074/jbc.M205627200
Lorenz, John N. ; Baird, Nancy R. ; Judd, Louise M. ; Noonan, William T. ; Andringa, Anastasia ; Doetschman, Thomas C ; Manning, Patrice A. ; Liu, Lynne H. ; Miller, Marian L. ; Shull, Gary E. / Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 40. pp. 37871-37880.
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AU - Judd, Louise M.

AU - Noonan, William T.

AU - Andringa, Anastasia

AU - Doetschman, Thomas C

AU - Manning, Patrice A.

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AU - Shull, Gary E.

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