Abstract |
Mutations in the human gene that encodes the AE1 Cl(-)/HCO(3)(-) 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(-)/HCO(3)(-) 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(-)/HCO(3)(-) exchanger is required for maintenance of normal acid-base homeostasis by distal renal regeneration of bicarbonate in the mouse as well as in humans.
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Authors | Paul A Stehberger, Boris E Shmukler, Alan K Stuart-Tilley, Luanne L Peters, Seth L Alper, Carsten A Wagner |
Journal | Journal of the American Society of Nephrology : JASN
(J Am Soc Nephrol)
Vol. 18
Issue 5
Pg. 1408-18
(May 2007)
ISSN: 1046-6673 [Print] United States |
PMID | 17409310
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anion Exchange Protein 1, Erythrocyte
- Antiporters
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Topics |
- Acid-Base Imbalance
(blood, urine)
- Acidosis, Renal Tubular
(blood, complications, genetics, urine)
- Animals
- Anion Exchange Protein 1, Erythrocyte
(genetics, metabolism)
- Antiporters
(genetics, metabolism)
- Female
- Gene Expression Profiling
- Hydrogen-Ion Concentration
- Kidney
(pathology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nephrocalcinosis
(etiology, pathology)
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