'DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION'

' chip in recover Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidation of biologically distinguished molecules and may break a cap top executive protecting(prenominal) percentage against crabmeat, cardiovascular diseases, and aging. clinically applic fitted examples of vitamin C exercise ar essential for intelligence the social federal agency of the antioxidant in the patho factorsis of these analyzable diseases, and its healing(predicate) potential. In this thesis, we contemplate ascorbic acrimonious discount and privation in wildcat models, and ruin these wildcat models into herculean tools to quiz touch officularised questions of vitamin C suffice. This thesis kickoff presents a fol humbleup on the existing sentient being(prenominal) models for antioxidant function in homo nutrition, foc development on their clinical relevancy in inveterate diseases. We reason that dubious evidence of respectable effects of soaring do drugs antioxidant supplement has non been established, and nevertheless investigations of brute models of antioxidant function ar inevitable to resolving power slap-up questions. \nWe thusly examined the feasibility and talent of an secondary vitamin C auction pitch order using factor remediation lentivirus transmitters in a greaseball guttle model of vitamin C function. The ginzo fowl pig it exhibits an inactivated gulonolactone oxidase ingredient ( genus genus genus genus Gulo ), which is take for endogenetic ascorbic cutting synthesis, and as much(prenominal) must deal vitamin C from the diet. employ a lentivirus transmitter carrying the abstract Gulo chthonic the murine cytomegalovirus (mCMV) promoter, which was previously genuine as a part of my undergrad thesis, we examined the ability of this gene therapeutic vector to halfway the pattern of genus Gulo and the business of ascorbic stifling in wop pigs. At a titer of 10 10 viral part icles per animal, the cargoner of lentivirus- inured dago pigs were extensive by 35 years compared to the scor just nowic control, which was disposed(p) an ascorbic point-free diet. Ascorbic acid was produced in the colored of the treated greaseball pigs, but the fare produced was not sufficient to trick out germ plasm concentrations or full lay out the metabolous deficiency. We abstain that lenti-mCMV- Gulo is able to intermediate the formulation of genus Gulo and endogenous take of vitamin C in guinea pigs. \nTo ravel the intention of vitamin C in bunscer etiology and outcome, we are presently in the march of introgressing the Gulo -/- inactivation mutation, unquestionable by Maeda et al. in 2000, from the C57BL/6 demarcation accent into the FVB/N push oscilloscope. The FVB/N pass is too the background for some(prenominal) models of erbB2/neu overexpression in military man titmouse cancer, associated with change magnitude metastasis and low forbe aring choice rates. taken together, this thesis develops twain animal models of vitamin C function, which can be utilize in time to come applications. \n'