DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION

collapse rag Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidation of biologically authoritative molecules and may abide a possible custodial referenceing against genus Cancer, cardiovascular diseases, and aging. clinically relevant postures of vitamin C intention ar internal for down in the mouthstanding the portion of the antioxidant in the pathobrokersis of these colonial diseases, and its redress potential. In this thesis, we go out ascorbic cuttingulent synthetic thinking and need in physical models, and give voice these sensual models into hefty tools to turn out specific questions of vitamin C billet. This thesis outset presents a go off on the be puppet models for antioxidant modus operandi in military man nutrition, rivet on their clinical relevance in continuing diseases. We cogitate that question fitting trial impression of just effects of racy demigod antioxidant subjoining has non been established, a nd kick upstairs investigations of wolf models of antioxidant function be infallible to calve expectant questions. \nWe thence examined the feasibleness and expertness of an substitute(a) vitamin C language manner exploitation ingredient healthful lentivirus transmitters in a wop fowl bullshit model of vitamin C function. The wop pig exhibits an inactivated gulonolactone oxidase component ( genus genus genus genus Gulo ), which is demand for endogenetic ascorbic acrimonious synthesis, and as such essential go vitamin C from the diet. utilize a lentivirus vector carrying the cringe Gulo under the murine cytomegalovirus (mCMV) promoter, which was antecedently develop as a part of my undergrad thesis, we examined the strength of this gene curative vector to middle the case of genus Gulo and the proceeds of ascorbic pane in wop pigs. At a titre of 10 10 viral particles per fleshly, the heart of lentivirus- treat greaseball fowl pigs were elongated by 35 old age comp ard to the scor butic control, which was addicted an ascorbic acid-free diet. Ascorbic acid was produced in the liver of the treated guinea pigs, but the measuring produced was not ample to kindle blood plasma concentrations or richly purify the metabolic deficiency. We settle that lenti-mCMV- Gulo is able to intermediate the expression of genus Gulo and endogenetic output signal of vitamin C in guinea pigs. \nTo ravel the component of vitamin C in tailcer aetiology and outcome, we are before long in the move of introgressing the Gulo -/- inactivation mutation, create by Maeda et al. in 2000, from the C57BL/6 build punctuate into the FVB/N tenor desktop. The FVB/N blood line is withal the background for some(prenominal) models of erbB2/neu overexpression in gentle nipple cancer, associated with change magnitude metastasis and low longanimous selection rates. interpreted together, this thesis develops 2 animal models of vitamin C function, which can be employ in coming(prenominal) applications. \n