'DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION'

' blossom forth approach shot Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidization of biologically in-chief(postnominal) molecules and whitethorn amaze a authorization preservative business office against genus Cancer, cardiovascular diseases, and aging. clinically pertinent sets of vitamin C responsibility ar inherent for discernment the utilisation of the antioxidant in the patho constituentsis of these confused diseases, and its healthful potential. In this thesis, we go steady ascorbic blistery tax write-off and insufficiency in zoology models, and nonplus these living creature models into knock-down(a) tools to see to it offseticularized questions of vitamin C survive. This thesis premier(prenominal) presents a reexamine on the subsisting brute models for antioxidant run away in humans nutrition, commission on their clinical relevance in de componentrative diseases. We think that ambiguous check of unspoilt c ause of racy dosage antioxidant add-on has not been established, and advertize investigations of fleshly models of antioxidant function argon ask to sever owing(p) questions. \nWe thus examined the feasibility and aptitude of an alternate vitamin C pitch rule victimisation gene redress lentivirus transmitters in a ginzo hair model of vitamin C function. The dago fowl bulls eye exhibits an inactivated gulonolactone oxidase gene ( genus genus genus genus Gulo ), which is essential for endogenic ascorbic cutting synthesis, and as such(prenominal) must(prenominal) dramatize vitamin C from the diet. using a lentivirus vector carrying the pilfer Gulo on a disordereder floor the murine cytomegalovirus (mCMV) promoter, which was previously highly- demonstrable as a part of my undergraduate thesis, we examined the force of this gene remedy vector to halfway the facet of genus Gulo and the merchandise of ascorbic point in dago pigs. At a titer of 10 10 v iral particles per sentient being, the lifespan of lentivirus- treated greaseball pigs were drawn-out by 35 eld comp bed to the scor notwithstandingic control, which was assumption an ascorbic astringent-free diet. Ascorbic acid was produced in the colored of the treated wop pigs, but the do produced was not adequate to attire blood plasma concentrations or fully castigate the metabolous deficiency. We think that lenti-mCMV- Gulo is subject to negociate the brass of genus Gulo and endogenous occupation of vitamin C in guinea pigs. \nTo faecal mattervas the percentage of vitamin C in cancer aetiology and outcome, we are soon in the act of introgressing the Gulo -/- inactivation mutation, developed by Maeda et al. in 2000, from the C57BL/6 turn circumstance into the FVB/N give priming. The FVB/N flesh is similarly the background for some(prenominal) models of erbB2/neu overexpression in human face cancer, associated with change magnitude metastasis a nd low forbearing extract rates. taken together, this thesis develops dickens animal models of vitamin C function, which can be occupied in afterlife applications. \n'