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Permanent link (DOI): https://doi.org/10.7939/R39S77

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Advancing the Alb-uPA/SCID/Bg Chimeric Mouse Open Access

Descriptions

Other title
Subject/Keyword
Hepatitis C
Mouse Model
Transgenic mice
Alb-uPA/SCID/Beige mouse
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Hsi Dickie, Belinda
Supervisor and department
Elliot, John F (Medical Microbiology and Immunology)
Kneteman, Norman M (Surgery)
Tyrell, D. Lorne (Medical Microbiology and Immunology)
Examining committee member and department
Churchill, Thomas A (Surgery)
Humar, Atul (Medicine)
Kay, Mark A (Department of Pediatrics and Genetics, Stanford University)
Department
Department of Surgery
Specialization

Date accepted
2009-10-02T22:08:31Z
Graduation date
2009-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
The feasibility of the Alb-uPA/SCID/Bg chimeric mouse as a model for Hepatitis C Virus (HCV) infection was assessed experimentally by (1) the infection and treatment with another hepatotropic virus, Hepatitis B Virus (HBV) and (2) the infection of the model with HCV and the subsequent treatment of that infection with a pro-apoptotic factor (BID) targeted to infected hepatocytes. In the former, the infected mouse responded favorably, and in the manner of human patients, to a standard imunoglobulin therapy. In the latter, HCV-infected hepatocytes were successfully targeted for cell death, with repeated doses of Adenovirus-delivered BID being the most effective at inhibiting virus spread. Efficacy and toxic side-effects of BID treatment could be reconciled by modulating the timing between doses, the most effective tested being three doses of BID at 7-day intervals. Analyses of chimeric model production were undertaken to improve the quality of human hepatocyte engraftment (typically only 25-35% of mice receiving grafts are currently used experimentally). Minor variations in success rates were experienced with respect to donor age or health status, or the age of recipient mice within an operational window of 5 to 13 days from birth. The greatest obstacle to useful engraftment (aside from technical challenges) was deemed to be the genetic/cellular integrity of the recipient mouse. This conclusion was based on variable engraftment success with ‘healthy’ donor cell preparations and a consideration of variability in immune deficiency arising in mice within a SCID/Bg mouse colony.
Language
English
DOI
doi:10.7939/R39S77
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File title: Table of Contents
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Page count: 184
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