Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6

Abstract

Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70–80% of kidney stones1, and small changes in urinary oxalate concentration affect the risk of stone formation2. SLC26A6 is an anion exchanger expressed on the apical membrane in many epithelial tissues, including kidney and intestine3,4,5,6. Among its transport activities, SLC26A6 mediates Cl-oxalate exchange5,6,7,8,9. Here we show that mutant mice lacking Slc26a6 develop a high incidence of calcium oxalate urolithiasis. Slc26a6-null mice have significant hyperoxaluria and elevation in plasma oxalate concentration that is greatly attenuated by dietary oxalate restriction. In vitro flux studies indicated that mice lacking Slc26a6 have a defect in intestinal oxalate secretion resulting in enhanced net absorption of oxalate. We conclude that the anion exchanger SLC26A6 has a major constitutive role in limiting net intestinal absorption of oxalate, thereby preventing hyperoxaluria and calcium oxalate urolithiasis.

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Figure 1: Targeted disruption of the Slc26a6 gene.
Figure 2: Transport activities in renal brush border membrane vesicles from wild-type and Slc26a6-null mice.
Figure 3: Urolithiasis phenotype in Slc26a6-null mice.
Figure 4: Abnormal oxalate homeostasis in Slc26a6-null mice.

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Acknowledgements

This work was supported by US National Institutes of Health grants DK33793, DK17433, DK56788 and DK60699.

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Jiang, Z., Asplin, J., Evan, A. et al. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet 38, 474–478 (2006). https://doi.org/10.1038/ng1762

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