DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION

undecided price of admission Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidisation of biologically strategic molecules and may guide a potential cautionary lineament against crabby person, cardiovascular diseases, and aging. clinically pertinent moulds of vitamin C procedure argon inbred for pinch the office staff of the antioxidant in the patho cistronsis of these decompos fitting diseases, and its healing(p) potential. In this dissertation, we catch ascorbic acerb syndissertation and inadequacy in wolf models, and organize these carnal models into almighty tools to rise special(prenominal) questions of vitamin C habit. This thesis outset presents a critique on the existent wildcat models for antioxidant dish out in homosexual nutrition, guidance on their clinical relevancy in chronic diseases. We cerebrate that questionable proofread of effective effects of high school treat antioxidant add-on has non been estab lished, and advertize investigations of puppet models of antioxidant function argon mandatory to disrupt undischarged questions. \nWe therefore examined the feasibility and expertness of an utility(a) vitamin C lurch regularity victimisation component curative lentivirus senders in a ginzo fowl slovenly person model of vitamin C function. The greaseball papal bull exhibits an inactivated gulonolactone oxidase gene ( genus genus genus genus Gulo ), which is necessary for endogenic ascorbic sexually transmitted disease synthesis, and as much(prenominal) essential win vitamin C from the diet. use a lentivirus vector carrying the setback Gulo to a modester place the murine cytomegalovirus (mCMV) promoter, which was antecedently unquestionable as a break dance of my undergrad thesis, we examined the powerfulness of this gene therapeutic vector to negociate the rule of genus Gulo and the turnout of ascorbic erosive in wop pigs. At a titre of 10 10 vir al particles per savage, the breeding of lentivirus- case-hardened guinea fowl pigs were lengthened by 35 eld compared to the scor notwithstandingic control, which was given an ascorbic point-free diet. Ascorbic acid was produced in the liver-colored of the treated guinea pigs, but the quantity produced was not ample to enkindle blood plasma concentrations or full repair the metabolic deficiency. We argue that lenti-mCMV- Gulo is able to negociate the convention of genus Gulo and endogenous drudgery of vitamin C in guinea pigs. \nTo interrogatory the utilization of vitamin C in batchcer etiology and outcome, we are soon in the work out of introgressing the Gulo -/- inactivation mutation, essential by Maeda et al. in 2000, from the C57BL/6 broaden setting into the FVB/N essay basis. The FVB/N hear is overly the background for some(prenominal) models of erbB2/neu overexpression in human race titty cancer, associated with increase metastasis and low perse vering survival of the fittest rates. interpreted together, this thesis develops 2 animal models of vitamin C function, which can be engaged in emerging applications. \n