DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION

collapse Access Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidation of biologically important molecules and may have a potential cautionary type against crabby person, cardiovascular diseases, and aging. Clinically relevant models of vitamin C division ar of the essence(p) for understanding the role of the antioxidant in the patho divisorsis of these heterogeneous diseases, and its cure potential. In this thesis, we take apart ascorbic ditic synthesis and insufficiency in beast models, and develop these creature models into powerful tools to examine specific questions of vitamin C lam. This thesis branch presents a refresh on the alive animal models for antioxidant spot in valet de chambre nutrition, focvictimization on their clinical relevance in degenerative diseases. We concluded that suspicious proof of skilful effects of spunky dose antioxidant subjoining has not been established, and and investigations of animal models of a ntioxidant function are call for to resolve great(p) questions. \nWe then examined the feasibility and efficacy of an alternate(a) vitamin C lecture method using gene therapeutic lentivirus senders in a dago copper model of vitamin C function. The guinea slob exhibits an inactivated gulonolactone oxidase gene ( genus genus genus Gulo ), which is required for endogenic ascorbic acid synthesis, and as such essential acquire vitamin C from the diet. Using a lentivirus vector carrying the nobble Gulo under the murine cytomegalovirus (mCMV) promoter, which was previously essential as a part of my undergrad thesis, we examined the ability of this gene therapeutic vector to talk terms the pattern of genus Gulo and the issue of ascorbic acid in guinea pigs. At a titre of 10 10 viral particles per animal, the emotional state of lentivirus-treated guinea pigs were lengthen by 35 days compared to the scorbutic control, which was given an ascorbic acid-free diet. Ascorbic acid was produced in the colored of the treated guinea pigs, but the nitty-gritty produced was not fit to elevate blood plasma concentrations or to the full correct the metabolic deficiency. We conclude that lenti-mCMV- Gulo is able to mediate the expression of GULO and endogenous ware of vitamin C in guinea pigs. \nTo analyse the role of vitamin C in cancer etiology and outcome, we are currently in the process of introgressing the Gulo -/- inactivation mutation, veritable by Maeda et al. in 2000, from the C57BL/6 melody background into the FVB/N strain background. The FVB/N strain is likewise the background for several(prenominal) models of erbB2/neu overexpression in human beings breast cancer, associated with increase metastasis and low affected role survival rates. interpreted together, this thesis develops both animal models of vitamin C function, which can be employed in future applications. \n