2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Data Supplements All Versions of this Article: ASN.2006101072v1 18/5/1408    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stehberger, P. A. Articles by Wagner, C. A. Search for Related Content PubMed PubMed Citation Articles by Stehberger, P. A. Articles by Wagner, C. A. Related Collections Related Article

Distal Renal Tubular Acidosis in Mice Lacking the AE1 (Band3) Cl^–/HCO₃^– Exchanger (slc4a1)

Paul A. Stehberger^*, Boris E. Shmukler, Alan K. Stuart-Tilley, Luanne L. Peters, Seth L. Alper^, and Carsten A. Wagner^*

^* Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Molecular and Vascular Medicine Unit and Renal Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; and Jackson Laboratories, Bar Harbor, Maine

Address correspondence to: Dr. Carsten A. Wagner, Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-807 Zurich, Switzerland. Phone: +41-44-63-50569; Fax: +41-44-63-56814; E-mail: wagnerca{at}access.unizh.ch

Received for publication October 2, 2006. Accepted for publication February 14, 2007.

Mutations in the human gene that encodes the AE1 Cl^–/HCO₃^– exchanger (SLC4A1) cause autosomal recessive and dominant forms of distal renal tubular acidosis (dRTA). A mouse model that lacks AE1/slc4a1 (slc4a1–/–) exhibited dRTA characterized by spontaneous hyperchloremic metabolic acidosis with low net acid excretion and, inappropriately, alkaline urine without bicarbonaturia. Basolateral Cl^–/HCO₃^– exchange activity in acid-secretory intercalated cells of isolated superfused slc4a1–/– medullary collecting duct was reduced, but alternate bicarbonate transport pathways were upregulated. Homozygous mice had nephrocalcinosis associated with hypercalciuria, hyperphosphaturia, and hypocitraturia. A severe urinary concentration defect in slc4a1–/– mice was accompanied by dysregulated expression and localization of the aquaporin-2 water channel. Mice that were heterozygous for the AE1-deficient allele had no apparent defect. Thus, the slc4a1–/– mouse is the first genetic model of complete dRTA and demonstrates that the AE1/slc4a1 Cl^–/HCO₃^– exchanger is required for maintenance of normal acid-base homeostasis by distal renal regeneration of bicarbonate in the mouse as well as in humans.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2007 18: 1363-1364. [Full Text] [PDF]

This article has been cited by other articles:

				M. Nowik, M. R. Lecca, A. Velic, H. Rehrauer, A. W. Brandli, and C. A. Wagner Genome-wide gene expression profiling reveals renal genes regulated during metabolic acidosis Physiol Genomics, February 19, 2008; 32(3): 322 - 334. [Abstract] [Full Text] [PDF]

				N. Mohebbi, J. Kovacikova, M. Nowik, and C. A. Wagner Thyroid hormone deficiency alters expression of acid-base transporters in rat kidney Am J Physiol Renal Physiol, July 1, 2007; 293(1): F416 - F427. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673