Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice

Dawson, Paul A., Russell, Christopher S., Lee, Soohyun, McLeay, Sarah C., van Dongen, Jacobus M., Cowley, David M., Clarke, Lorne A. and Markovich, Daniel (2010) Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice. Journal of Clinical Investigation, 120 3: 706-712. doi:10.1172/JCI31474

Author Dawson, Paul A.
Russell, Christopher S.
Lee, Soohyun
McLeay, Sarah C.
van Dongen, Jacobus M.
Cowley, David M.
Clarke, Lorne A.
Markovich, Daniel
Title Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 2010-03-01
Sub-type Article (original research)
DOI 10.1172/JCI31474
Open Access Status DOI
Volume 120
Issue 3
Start page 706
End page 712
Total pages 7
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Formatted abstract
Urolithiasis, a condition in which stones are present in the urinary system, including the kidneys and bladder, is a poorly understood yet common disorder worldwide that leads to significant health care costs, morbidity, and work loss. Acetaminophen-induced liver damage is a major cause of death in patients with acute liver failure. Kidney and urinary stones and liver toxicity are disturbances linked to alterations in oxalate and sulfate homeostasis, respectively. The sulfate anion transporter-1 (Sat1; also known as Slc26a1) mediates epithelial transport of oxalate and sulfate, and its localization in the kidney, liver, and intestine suggests that it may play a role in oxalate and sulfate homeostasis. To determine the physiological roles of Sat1, we created Sat1-/- mice by gene disruption. These mice exhibited hyperoxaluria with hyperoxalemia, nephrocalcinosis, and calcium oxalate stones in their renal tubules and bladder. Sat1-/- mice also displayed hypersulfaturia, hyposulfatemia, and enhanced acetaminophen-induced liver toxicity. These data suggest that Sat1 regulates both oxalate and sulfate homeostasis and may be critical to the development of calcium oxalate urolithiasis and hepatotoxicity.
Copyright © 2010, American Society for Clinical Investigation.

Keyword Brush border
Sulfate transporters
Transcriptional regulation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 47 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 21 Mar 2010, 10:05:58 EST