Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6

Zhirong Jiang, John R. Asplin, Andrew Evan, Vazhaikkurichi M. Rajendran, Heino Velazquez, Timothy P. Nottoli, Henry J. Binder, Peter S. Aronson

Research output: Contribution to journalArticle

192 Citations (Scopus)

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 intestine3-6. Among its transport activities, SLC26A6 mediates Cl--oxalate exchange5-9. 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.

Original languageEnglish
Pages (from-to)474-478
Number of pages5
JournalNature Genetics
Volume38
Issue number4
DOIs
StatePublished - Apr 2006

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Oxalates
Anions
Hyperoxaluria
Intestinal Secretions
Kidney
Urologic Diseases
Calcium Oxalate
Urolithiasis
Intestinal Absorption
Calcium Oxalate Nephrolithiasis
Epithelium
Membranes
Incidence

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Jiang, Z., Asplin, J. R., Evan, A., Rajendran, V. M., Velazquez, H., Nottoli, T. P., ... Aronson, P. S. (2006). Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nature Genetics, 38(4), 474-478. https://doi.org/10.1038/ng1762

Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. / Jiang, Zhirong; Asplin, John R.; Evan, Andrew; Rajendran, Vazhaikkurichi M.; Velazquez, Heino; Nottoli, Timothy P.; Binder, Henry J.; Aronson, Peter S.

In: Nature Genetics, Vol. 38, No. 4, 04.2006, p. 474-478.

Research output: Contribution to journalArticle

Jiang, Z, Asplin, JR, Evan, A, Rajendran, VM, Velazquez, H, Nottoli, TP, Binder, HJ & Aronson, PS 2006, 'Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6', Nature Genetics, vol. 38, no. 4, pp. 474-478. https://doi.org/10.1038/ng1762
Jiang Z, Asplin JR, Evan A, Rajendran VM, Velazquez H, Nottoli TP et al. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nature Genetics. 2006 Apr;38(4):474-478. https://doi.org/10.1038/ng1762
Jiang, Zhirong ; Asplin, John R. ; Evan, Andrew ; Rajendran, Vazhaikkurichi M. ; Velazquez, Heino ; Nottoli, Timothy P. ; Binder, Henry J. ; Aronson, Peter S. / Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. In: Nature Genetics. 2006 ; Vol. 38, No. 4. pp. 474-478.
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