NDLI: Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wen, Donghai Yuan, Yang Cornelius, Ryan J. Li, Huaqing Warner, Paige C. Wang, Bangchen Wang-France, Jun Boettger, Thomas Sansom, Steven C.
Description	Author Affiliation: Wen D ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Yuan Y ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Cornelius RJ ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Li H ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Warner PC ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Wang B ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Wang-France J ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska); Boettger T ( Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.); Sansom SC ( Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska)
Abstract	In many circumstances, the pathogenesis of distal renal tubular acidosis (dRTA) is not understood. In the present study, we report that a mouse model lacking the electrogenic Na(+)-HCO3 (-) cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild-type mice, and its expression was significantly increased after acid loading. NBCe2 KO mice did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2 KO mice exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2 KO mice had decreased luminal transepithelial potential in the CNT, as revealed by micropuncture. Further immunofluorescence and Western blot experiments found that NBCe2 KO mice had increased expression of H(+)-ATPase B1 in the plasma membrane. These results showed that NBCe2 KO mice with acid loading developed increased urinary K(+) and Ca(2+) wasting due to decreased luminal transepithelial potential in the CNT. NBCe2 KO mice compensated to maintain systemic pH by increasing H(+)-ATPase in the plasma membrane. Therefore, defects in NBCe2 can cause dRTA, and NBCe2 has an important role to regulate urinary acidification and the transport of K(+) and Ca(2+) in the distal nephron.
File Format	HTM / HTML
ISSN	1931857X
e-ISSN	15221466
DOI	10.1152/ajprenal.00163.2015
Journal	AJP: Renal Physiology
Issue Number	6
Volume Number	309
Language	English
Publisher	American Physiological Society
Publisher Date	2015-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Cell Membrane Chlorine Mice, Inbred C57bl Discipline Nephrology Metabolism Mice, Knockout Membrane Proteins Discipline Physiology Kidney Tubules, Distal Animals Hypercalciuria Sodium-bicarbonate Symporters Acidosis, Renal Tubular Hypokalemia Proton-translocating Atpases Genetics Physiology Mice
Content Type	Text
Resource Type	Article
Subject	Physiology Urology

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