SLC2A9 (GLUT9) mediates urate reabsorption in the mouse kidney.

TitreSLC2A9 (GLUT9) mediates urate reabsorption in the mouse kidney.
Publication TypeJournal Article
Year of Publication2018
AuthorsAuberson, M, Stadelmann, S, Stoudmann, C, Seuwen, K, Koesters, R, Thorens, B, Bonny, O
JournalPflügers Archiv - European Journal of Physiology
Pagination1-13
Date Published08/2018
DOI10.1007/s00424-018-2190-4
ISSN1432-2013
Abstract

Uric acid (UA) is a metabolite of purine degradation and is involved in gout flairs and kidney stones formation. GLUT9 (SLC2A9) was previously shown to be a urate transporter in vitro. In vivo, humans carrying GLUT9 loss-of-function mutations have familial renal hypouricemia type 2, a condition characterized by hypouricemia, UA renal wasting associated with kidney stones, and an increased propensity to acute renal failure during strenuous exercise. Mice carrying a deletion of GLUT9 in the whole body are hyperuricemic and display a severe nephropathy due to intratubular uric acid precipitation. However, the precise role of GLUT9 in the kidney remains poorly characterized. We developed a mouse model in which GLUT9 was deleted specifically along the whole nephron in a tetracycline-inducible manner (subsequently called kidney-inducible KO or kiKO). The urate/creatinine ratio was increased as early as 4 days after induction of the KO and no GLUT9 protein was visible on kidney extracts. kiKO mice are morphologically identical to their wild-type littermates and had no spontaneous kidney stones. Twenty-four-hour urine collection revealed a major increase of urate urinary excretion rate and of the fractional excretion of urate, with no difference in urate concentration in the plasma. Polyuria was observed, but kiKO mice were still able to concentrate urine after water restriction. KiKO mice displayed lower blood pressure accompanied by an increased heart rate. Overall, these results indicate that GLUT9 is a crucial player in renal handling of urate in vivo and a putative target for uricosuric drugs.

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/30105595?dopt=Abstract

Alternate JournalPflugers Arch.
Citation Key / SERVAL ID9069
Peer reviewRefereed
PubMed ID30105595
Grant List310030-163340 / / Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung /
PP00P3-133648 / / Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung /

                         

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