{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:41:26Z","timestamp":1781091686615,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T00:00:00Z","timestamp":1328140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p><jats:bold>Organisms using oxygen for aerobic respiration require antioxidants to balance the production of reactive oxygen species during metabolic processes. Various species \u2013 including humans and other primates \u2013 suffer mutations in the <jats:italic>GULO<\/jats:italic> gene encoding <jats:italic>L<\/jats:italic>\u2010gulono\u2010<jats:italic>\u03b3<\/jats:italic>\u2010lactone oxidase; GULO is the rate\u2010limiting enzyme in the biosynthesis of ascorbate, an important cellular antioxidant. Animals lacking the ability to synthesize vitamin C develop scurvy without dietary supplementation. The <jats:italic>Gulo(<\/jats:italic>\u2212<jats:italic>\/<\/jats:italic>\u2212<jats:italic>)<\/jats:italic> knockout (KO) mouse requires oral supplemental vitamin C; without this supplementation the animal dies with a scorbutic condition within several weeks. Vitamin C is known to be most abundant in the brain, where it is believed to play important roles in neuroprotection, neurotransmission and neuromodulation. We therefore hypothesized that ascorbate deficiency in <jats:italic>Gulo(<\/jats:italic>\u2212<jats:italic>\/<\/jats:italic>\u2212<jats:italic>)<\/jats:italic> KO mice might lead to an abnormal behavioral phenotype. We established the amount of ascorbate in the drinking water (220 ppm) necessary for generating a chronic low\u2010ascorbate status in the brain, yet clinically the mice appeared healthy throughout 100 days postpartum at which time all behavioral\u2010phenotyping tests were completed. Compared with <jats:italic>Gulo(<\/jats:italic>+<jats:italic>\/<\/jats:italic>+<jats:italic>)<\/jats:italic> wild\u2010type littermates, ascorbate\u2010deficient <jats:italic>Gulo(<\/jats:italic>\u2212<jats:italic>\/<\/jats:italic>\u2212<jats:italic>)<\/jats:italic> mice were found to be less active in moving in their environment; when in water, these mice swam more slowly in some tests, consistent with a mild motor deficit. We found no evidence of cognitive, anxiety or sensorimotor\u2010gating problems. Despite being less active, <jats:italic>Gulo(<\/jats:italic>\u2212<jats:italic>\/<\/jats:italic>\u2212<jats:italic>)<\/jats:italic> mice exhibited exaggerated hyperactivity to the dopaminergic agonist methamphetamine. The subnormal movement, combined with hypersensitivity to a dopamine agonist, point to developmental ascorbate deficiency causing long\u2010term striatal dysfunction.<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.1601-183x.2011.00762.x","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T08:14:28Z","timestamp":1328170468000},"page":"269-277","source":"Crossref","is-referenced-by-count":34,"title":["Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of <i>Gulo(<\/i>\u2212<i>\/<\/i>\u2212<i>)<\/i> knockout mice"],"prefix":"10.1111","volume":"11","author":[{"given":"Y.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. P.","family":"Curran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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