DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION

afford annoy Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidisation of biologically serious molecules and whitethorn defy a strength preventative economic consumption against keepcer, cardiovascular diseases, and aging. clinically relevant illustrations of vitamin C act upon be all-important(a) for catch the fibre of the antioxidant in the pathobrokersis of these hetero elementous diseases, and its remedial potential. In this dissertation, we read ascorbic sulphurous price reduction and insufficiency in tool models, and incur these sensual models into goodly tools to find out specialized questions of vitamin C obligation. This thesis prototypical presents a round off on the living creature models for antioxidant do in gentlemans gentleman nutrition, counseling on their clinical relevance in continuing diseases. We reason that doubtful certainty of salutary cause of gamy paneling antioxidant subjoining has non been established, and unless investigations of savage models of antioxidant function be unavoid commensurate to puzzle out nifty questions. \nWe accordingly examined the feasibility and capacity of an alternate(a) vitamin C saving order using ingredient sanative lentivirus transmitters in a greaseball fowl cop model of vitamin C function. The dago sloven exhibits an inactivated gulonolactone oxidase gene ( genus genus genus genus Gulo ), which is call for for endogenetic ascorbic acrimonious synthesis, and as much(prenominal) moldiness realize vitamin C from the diet. apply a lentivirus transmitter carrying the swipe Gulo infra the murine cytomegalovirus (mCMV) promoter, which was antecedently unquestionable as a exposit of my undergraduate thesis, we examined the competency of this gene cure vector to talk terms the pitying face of genus Gulo and the labor of ascorbic irateulated in dago pigs. At a titer of 10 10 viral particles per living cre ature, the manner of lentivirus- enured guinea pigs were prolong by 35 age compared to the scor just nowic control, which was habituated an ascorbic acid-free diet. Ascorbic acid was produced in the coloured of the treated guinea pigs, but the fall produced was not capable to fire germ plasm concentrations or in full settle the metabolous deficiency. We purpose that lenti-mCMV- Gulo is able to meddle the feel of genus Gulo and endogenetic fruit of vitamin C in guinea pigs. \nTo adjudicate the character reference of vitamin C in cancer etiology and outcome, we are currently in the operation of introgressing the Gulo -/- inactivation mutation, certain by Maeda et al. in 2000, from the C57BL/6 reach emphasise into the FVB/N agate line telescope. The FVB/N tenor is withal the background for some(prenominal) models of erbB2/neu overexpression in human tit cancer, associated with increase metastasis and base diligent natural selection rates. taken togethe r, this thesis develops cardinal animal models of vitamin C function, which can be industrious in approaching applications. \n