Kidney and Intestine Transport Defects in Slc26a6 Null Mice

SLC26A6 (PAT1, CFEX) is an anion exchanger that is expressed on the apical membrane of kidney proximal tubule and small intestine. Modes of transport mediated by SLC26A6 include Cl-formate exchange, Cl-HCO3 exchange and Cl-oxalate exchange. To study its role in kidney and intestine physiology, gene targeting was used to prepare mice lacking Slc26a6. Homozygous mutant Slc26a6(-/-) mice appeared healthy and exhibited normal blood pressure, kidney function and plasma electrolyte profile. In proximal tubules microperfused with a low bicarbonate-high chloride solution, the baseline rate of fluid absorption (Jv), an index of NaCl transport under these conditions, was the same in wild-type and null mice. However, the stimulation of Jv by oxalate observed in wild-type mice was completely abolished in Slc26a6 null mice (p < 0.05). Formate stimulation of Jv was partially reduced in null mice but the difference from the response in wild-type mice did not reach statistical significance. Apical membrane chloride-base exchange activity, assayed with the pH sensitive dye BCPCF in microperfused proximal tubules, was decreased by 58% in Slc26a6-/animals (p<0.001 vs. wild-types). In the duodenum, the baseline rate of bicarbonate secretion, measured in mucosal tissue mounted in Ussing chambers, was decreased by ~30% (p<0.03), whereas the forskolin-stimulated component of bicarbonate secretion was the same in wild-type and Slc26a6-/mice. We conclude that Slc26a6 mediates oxalate-stimulated NaCl absorption and also contributes to apical membrane Cl-base exchange in the kidney proximal tubule; it also plays an important role in bicarbonate secretion in the duodenum.