Ascorbic acid, an essential vitamin in humans, is a necessary cofactor in collagen and catecholamine metabolism. In order to assess the role of ascorbic acid in normal cellular function and development, we have created mice deficient in the ascorbic acid transporter Slc23a1 (Svct2) by deleting exons encoding residues 218-281 and creating a frame-shift mutation. The deletion allele reduces uptake of 14C-labeled ascorbic acid by >95% in cultured embryonic fibroblasts (2.19 microM/min in +/+ versus 0.12 micromole/min in -/- cells). Ascorbic acid levels were undetectable in the brains, pituitary glands, and adrenal glands of E19.5-20.5 fetuses and of newborn mutant mice. Levels were also markedly reduced in the blood and kidney. Supplementation of pregnant females with enteral ascorbic acid or parenteral dehydroascorbic acid caused elevations of fetal blood ascorbic acid levels in +/+ and +/- fetuses but not in -/- fetuses, suggesting a role for Slc23a1 in placental transport of ascorbic acid as well. Homozygous -/- mice died within the first few minutes after birth with fulminant subependymal and periventricular hemorrhage. Autopsy revealed failure of lung expansion, although histological examination of lung was normal at the level of light microscopy. We conclude that Slc23a1 is the primary transporter for ascorbic acid into the central nervous system and adrenal gland and that failure to transport the compound normally is lethal in newborn mice. These mice demonstrate a previously unrecognized requirement for vitamin C in perinatal survival and should prove to be useful for assessing the role of ascorbic acid in development and neuroprotection.
| 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 |
