title: Recent applications of engineered animal antioxidant deficiency models in human nutrition and chronic disease.
abstract: Dietary antioxidants are essential nutrients that inhibit the oxidation of biologically important molecules and suppress the toxicity of reactive oxygen or nitrogen species. When the total antioxidant capacity is insufficient to quench these reactive species, oxidative damage occurs and contributes to the onset and progression of chronic diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancer. However, epidemiological studies that examine the relationship between antioxidants and disease outcome can only identify correlative associations. Additionally, many antioxidants also have prooxidant effects. Thus, clinically relevant animal models of antioxidant function are essential for improving our understanding of the role of antioxidants in the pathogenesis of complex diseases as well as evaluating the therapeutic potential and risks of their supplementation. Recent progress in gene knockout mice and virus-based gene expression has potentiated these areas of study. Here, we review the current genetically modified animal models of dietary antioxidant function and their clinical relevance in chronic diseases. This review focuses on the 3 major antioxidants in the human body: vitamin C, vitamin E, and uric acid. We examine genetic models of vitamin C synthesis (guinea pig, Osteogenic Disorder Shionogi rat, Gulo(-/-) and SMP30(-/-) mouse mutants) and transport (Slc23a1(-/-) and Slc23a2(-/-) mouse mutants), vitamin E transport (Ttpa(-/-) mouse mutant), and uric acid synthesis (Uox(-/-) mouse mutant). The application of these models to current research goals is also discussed.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Yu
authors.forename: Herb E
authors.initials: HE
authors.lastname: Schellhorn
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D001206:Ascorbic Acid Deficiency / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology; D003677:Deficiency Diseases / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D018384:Oxidative Stress; D014527:Uric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D014811:Vitamin E Deficiency / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D014527:Uric Acid