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SVCT1 (Slc23a1) knockout mice: Slc23a1 as the vitamin C kidney reabsorptive transporter
Author(s) -
Corpe Christopher,
Tu Hongbin,
Wang Jin,
Eck Peter,
Wang Yaohui,
Schnermann Jurgen,
FaulhaberWalter Robert,
Nussbaum Robert,
Levine Mark
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb111
Subject(s) - medicine , endocrinology , ascorbic acid , vitamin , vitamin c , excretion , chemistry , kidney , wild type , knockout mouse , weaning , transporter , biology , biochemistry , receptor , gene , mutant , food science
Vitamin C pharmacokinetics in humans indicate that the renal threshold of excretion is responsible for tightly controlled concentrations of the vitamin in plasma and accumulated in tissues. We hypothesized that Slc23a1, the vitamin C epithelial transporter expressed in kidney, is responsible for tight control. To test this we created a mouse null for the Slc23a1 gene. Inbred C57bL/6J wild type, Slc23a1+/− and Slc23a1−/− mice were generated on a Balb/c background. After weaning, growth rates of wild type, Slc23a1+/− and Slc23a1−/− mice were indistinguishable. Urine vitamin C fractional excretion was 7–10 fold higher in Slc23a1−/− mice compared to wildtype littermates. Corresponding plasma ascorbic acid concentrations in slc23a1−/− mice were 50–70% lower than in wild type littermates. In slc23a1−/− mice, neuronal tissue ascorbate concentrations levels were unaffected by the depressed plasma ascorbate levels, whereas all other tissues trended downwards. These data show that Slc23a1 is responsible for tight control of vitamin C, via regulation of renal threshold of excretion. The asymmetric response of tissues to decreased plasma vitamin C may represent redistribution of vitamin C to protect brain function. Humans with Slc23a1 polymorphisms that decrease transporter activity might have altered vitamin C pharmacokinetics due to a renal leak, and require additional vitamin C intake.