Abstract
A new transgenic mouse model for global increases in the Sodium Dependent Vitamin C transporter 2 (SVCT2) has been generated. The SVCT2-Tg mouse shows increased SVCT2 mRNA levels in all organs tested and correspondingly increased ascorbic acid (ASC) levels in all organs except liver. The extent of the increase in transporter mRNA expression differed among mice and among organs. The increased ASC levels did not have any adverse effects on behavior in the SVCT2-Tg mice, which did not differ from wild-type mice on tests of locomotor activity, anxiety, sensorimotor or cognitive ability. High levels of SVCT2 and ASC were found in the kidneys of SVCT2-Tg mice and urinary albumin excretion was lower in these mice than in wild-types. No gross pathological changes were noted in kidneys from SVCT2-Tg mice. SVCT2 immunoreactivity was detected in both SVCT2 and wild-type mice, and a stronger signal was seen in tubules than in glomeruli. Six treatments with Paraquat (3x10 and 3x15 mg/kg i.p.) were used to induce oxidative stress in mice. SVCT2-Tg mice showed a clear attenuation of Paraquat-induced oxidative stress in lung, as measured by F2-isoprostanes. Paraquat also decreased SVCT2 mRNA signal in liver, lung and kidney in SVCT2-Tg mice.
Highlights
IntroductionIn most mammals vitamin C (ascorbic acid; ASC) is synthesized in the liver
In most mammals vitamin C is synthesized in the liver
The data we present demonstrates successful generation of a new mouse model that expresses functional additional copies of the Sodium Dependent Vitamin C transporter 2 (SVCT2)
Summary
In most mammals vitamin C (ascorbic acid; ASC) is synthesized in the liver. Non-human primates, and guinea pigs the loss of action of the gulonolactone oxidase gene that is responsible for the last step in ASC synthesis from glucose leads to dependence on dietary intake of ASC to avoid scurvy. ASC is transported into the blood stream, cerebrospinal fluid and cells via the action of two specific vitamin C transporters – Sodium Dependent Vitamin C Transporters 1 and 2 (SVCT1 and SVCT2) [1,2,3]. SVCT1 and SVCT2 are differentially distributed among organs [3]. SVCT1 is mainly localized to epithelial cells in kidney, intestines and liver. SVCT2 is highly expressed in most other tissues including brain, lung, spleen and liver. The complete function, location and orientation of these transporters is still under investigation
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