Original ContributionLow vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2
Section snippets
SVCT2+/− mice
These mice were provided by Dr. Robert Nussbaum. Originally on the 129/SvEvTac background, they were backcrossed more than 10 generations to C57BL/6 mice to place them on this background. Animals were housed in breeding pairs in tub cages in a temperature- and humidity-controlled vivarium. Mice were kept on a 12:12-h light:dark cycle with lights on at 6:00 AM. Mice had free access to food and water for the duration of the experiment. Deionized water was supplemented with 0.33 g/L ascorbic acid
Genotype distribution among the litters
Using data from nine litters the genotype ratios were 12 (−/−):34 (+/−):31 (+/+). A χ2 test against the expected 1:2:1 ratio distribution was significant (χ2 = 10.428, p < 0.01, df = 2). Given 31 SVCT2+/+ mice, if Mendelian ratios were followed, then we would expect 31 SVCT2−/− and 62 SVCT2+/− mice. Separate χ2 tests revealed that both of these genotypes were underrepresented in the sample (χ2 > 11.64, p < 0.001).
Placenta
A gene-dosage effect was seen in VC levels such that for each additional copy of the SVCT2 a
Discussion
In contrast to a previous report [6], we found fewer than expected SVCT2−/− and SVCT2+/− mice in litters delivered by cesarean section, indicating that a smaller proportion of these fetuses survive until birth. This result suggests that lack of SVCT2, and therefore lack of VC in several major organs, contributes to fetal death. In both this and the earlier study [6] SVCT2+/− dams were supplemented with VC in the drinking water; however, the amounts given varied. In this study mice received 0.33 g
Acknowledgments
This work was supported by NIH Grant NS057674-03 to J.M.M. and NIH Grant DK59637 to the Lipid, Lipoprotein, and Atherosclerosis Core of the Vanderbilt Mouse Metabolic Phenotype Centers. The authors thank Lewis F. Pennock, Jr., for the photography of fetal brains.
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