RT Journal Article
SR Electronic
T1 Distal Renal Tubular Acidosis in Mice Lacking the AE1 (Band3) Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup> Exchanger (<em>slc4a1</em>)
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 1408
OP 1418
DO 10.1681/ASN.2006101072
VO 18
IS 5
A1 Stehberger, Paul A.
A1 Shmukler, Boris E.
A1 Stuart-Tilley, Alan K.
A1 Peters, Luanne L.
A1 Alper, Seth L.
A1 Wagner, Carsten A.
YR 2007
UL http://jasn.asnjournals.org/content/18/5/1408.abstract
AB 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.