Urate metabolism in urate transporter URAT1 transgenic mice

Tsukada Ai, Kimura Toru, Promsuk Jutabha, Anzai Naohiko, Ichida Kimiyoshi, Sakurai Hiroyuki

doi:10.6032/gnam.34.171

Urate is a final metabolite of purines and the major excretory organ is the kidney. Renal urate handling is clinically important because over-excretion and under-excretion of urate cause hypouricemia and hyperuricemia, respectively. We identified a urate-anion exchanger, URAT1, localized at the apical side in the renal proximal tubules. This transporter is likely to act on urate reabsorption, because URAT1 is a target for anti-gout drugs and mutation in URAT1 causes renal hypouricemia. Thus, URAT1 is one of the important molecules for maintaining the serum urate level. However, little is known about how URAT1 controls the serum urate level and its expression influences other urate transporters and urate metabolic enzymes in vivo. We constructed URAT1 transgenic mice (Tg) to investigate the urate transport mechanism in vivo. We used Tg mice for measurement of the urate concentration and DNA microarray and quantitative PCR analysis. RT-PCR showed that expression of Urat1 mRNA is specific in the kidney and the expression level in Tg mice was increased compared with that in wild type (WT) mice. Western blot and immunohistochemistry showed that exogenous URAT1 was expressed only in the renal proximal tubule cells in the kidney. Serum urate concentration in URAT1 Tg mice was not significantly different from that in WT mice. The urate level in urine from URAT1 Tg mice was the same as that from WT mice. DNA microarray and quantitative PCR analysis showed that in URAT1 Tg mice,the expression levels of urate metabolic enzymes and urate transporters other than Urat1 were the same as those in WT mice.

Urate metabolism in urate transporter URAT1 transgenic mice

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