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

Détails

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Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_789F1130AFFD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
SLC2A9 (GLUT9) mediates urate reabsorption in the mouse kidney.
Périodique
Pflugers Archiv
Auteur(s)
Auberson M., Stadelmann S., Stoudmann C., Seuwen K., Koesters R., Thorens B., Bonny O.
ISSN
1432-2013 (Electronic)
ISSN-L
0031-6768
Statut éditorial
Publié
Date de publication
12/2018
Peer-reviewed
Oui
Volume
470
Numéro
12
Pages
1739-1751
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, Blood Pressure, Female, Glucose Transport Proteins, Facilitative/genetics, Glucose Transport Proteins, Facilitative/metabolism, Heart Rate, Kidney/metabolism, Male, Mice, Mice, Inbred C57BL, Renal Reabsorption, Uric Acid/blood, Uric Acid/metabolism, Uric Acid/urine, GLUT9, Lithiasis, SLC2A9, Urate, Uric acid
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/08/2018 13:46
Dernière modification de la notice
28/09/2019 6:08
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