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

SLC2A9 (GLUT9) mediates urate reabsorption in the mouse kidney. Pflugers Arch. 2018 Aug 13;: Authors: Auberson M, Stadelmann S, Stoudmann C, Seuwen K, Koesters R, Thorens B, Bonny O 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 ura...
Source: Pflugers Archiv : European Journal of Physiology - Category: Physiology Authors: Tags: Pflugers Arch Source Type: research