The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modification that stabilize collagen3. We have created mice deficient in the mouse ortholog (Slc23a1) of a rat ascorbic acid transporter, Svct2. Cultured embryonic fibroblasts from Slc23a1-/- mice had <5% of normal ascorbic acid uptake. Ascorbic acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1-/- mice. Prenatal supplementation of pregnant females failed to elevate blood ascorbic acid in Slc23a1-/- fetuses, suggesting Slc23a1 is important in placental ascorbic acid transport. Homozygous Slc23a1-/- mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1-/- mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period. Animals carrying a """"""""floxed"""""""" allele of Slc23a1 have been made in order to carry out tissue-specific ablation of this gene.
| Bornstein, Stefan R; Yoshida-Hiroi, Mayumi; Sotiriou, Sotiria et al. (2003) Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2). FASEB J 17:1928-30 |
| Sotiriou, Sotiria; Gispert, Suzana; Cheng, Jun et al. (2002) Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med 8:514-7 |
| Gispert, S; Dutra, A; Lieberman, A et al. (2000) Cloning and genomic organization of the mouse gene slc23a1 encoding a vitamin C transporter. DNA Res 7:339-45 |
