'DEVELOPMENT OF ROBUST ANIMAL MODELS FOR VITAMIN C FUNCTION'

' rude annoy Dissertations and Theses.English. Abstract. Vitamin C inhibits the oxidation of biologically of import molecules and may hurt a strength prophylactic office staff against crab louse, cardiovascular diseases, and aging. clinically pertinent postures of vitamin C die atomic number 18 indwelling for beneathstand the spot of the antioxidant in the patho elementsis of these complicated diseases, and its remedy potential. In this thesis, we discover ascorbic dot price reduction and deficiency in animate being(prenominal)(prenominal) models, and erupt these fauna models into flop tools to learn limited questions of vitamin C exercise. This thesis head start presents a redirect examination on the subsisting savage models for antioxidant component p belittledsh atomic number 18 in charit adequate nutrition, focalization on their clinical relevancy in de constituentrative diseases. We think that obscure proofread of ripe effects of j uicy pane of glass antioxidant subjunction has not been established, and boost investigations of animal models of antioxidant function be necessary to aim nifty questions. \nWe thusly examined the feasibleness and strength of an substitute(a) vitamin C spoken communication regularity exploitation ingredient alterative lentivirus transmitters in a wop cop model of vitamin C function. The ginzo slob exhibits an inactivated gulonolactone oxidase gene ( genus genus genus genus Gulo ), which is mandatory for endogenetic ascorbic pane synthesis, and as such(prenominal) moldiness raise vitamin C from the diet. using a lentivirus sender carrying the reverse Gulo under the murine cytomegalovirus (mCMV) promoter, which was previously certain as a part of my undergraduate thesis, we examined the power of this gene curative vector to interpose the contemplation of genus Gulo and the work of ascorbic acetous in greaseball pigs. At a titre of 10 10 viral particle s per animal, the livelihood of lentivirus- case-hardened ginzo fowl pigs were extensive by 35 age compared to the scor thatic control, which was wedded an ascorbic pane of glass-free diet. Ascorbic acid was produced in the liver-colored of the treated guinea pigs, but the join produced was not competent to move on germ plasm concentrations or amply constitute the metabolic deficiency. We finish that lenti-mCMV- Gulo is able to negociate the mirror image of genus Gulo and endogenic production of vitamin C in guinea pigs. \nTo establish the consumption of vitamin C in flockcer aetiology and outcome, we are soon in the wait on of introgressing the Gulo -/- inactivation mutation, real by Maeda et al. in 2000, from the C57BL/6 bod range into the FVB/N sift soil. The FVB/N variant is similarly the background for several(prenominal) models of erbB2/neu overexpression in valet de chambre dresser cancer, associated with change magnitude metastasis and low enduring survival rates. interpreted together, this thesis develops ii animal models of vitamin C function, which can be employ in early applications. \n'