Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.
Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70-80% of kidney stones, and small changes in urinary oxalate concentration affect the risk of stone formation. SLC26A6 is an anion exchanger expressed on the apical membrane in many epithelial tissues, including kidney and intestine. Among its transport activities, SLC26A6 mediates Cl(-)-oxalate exchange. 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.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Zhirong
Z
Jiang
John R
JR
Asplin
Andrew P
AP
Evan
Vazhaikkurichi M
VM
Rajendran
Heino
H
Velazquez
Timothy P
TP
Nottoli
Henry J
HJ
Binder
Peter S
PS
Aronson
D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D002129:Calcium Oxalate / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051379:Mice; D018345:Mice, Knockout; D000076988:Sulfate Transporters; D014545:Urinary Calculi / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000652:urine
D017920:Antiporters; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D002129:Calcium Oxalate