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dc.contributor.advisorDuan, Dongshengeng
dc.contributor.authorBostick, Brian P., 1979-eng
dc.date.issued2010eng
dc.date.submitted2010 Falleng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on March 11, 2011).eng
dc.descriptionVita.eng
dc.descriptionThesis advisor: Dongsheng Duan.eng
dc.description"December 2010"eng
dc.descriptionPh. D. University of Missouri-Columbia 2010.eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Duchenne muscular dystrophy (DMD) is a fatal genetic muscle disease with no cure. DMD results from mutations in a critical muscle protein called dystrophin. Children born with DMD suffer severe muscle wasting leading to progressive weakness and paralysis. Patients usually die of respiratory or heart failure before the age of thirty. Gene therapy raises the hope of a cure for DMD heart disease. While significant strides have been made towards therapy for skeletal muscle disease, development of heart gene therapy lags behind. The seminal questions for realization of heart gene therapy of DMD include; developing an animal model, determining dosage, finding the correct gene, developing the vehicle for gene therapy and optimizing gene delivery. This dissertation details critical advancements towards gene therapy for DMD heart disease. First, we developed an animal model of DMD heart disease in the mdx mouse. We then determined that 50% mosaic dystrophin expression was sufficient to prevent DMD heart disease in this model. Next, we established that the truncated mini-dystrophin gene was capable of ameliorating DMD heart disease in the mdx mouse through cardiac specific transgenic expression. Then, we established the adeno-associated virus (AAV) as a vehicle for DMD heart gene therapy regardless of mouse age or the route of administration. Finally, we discovered that AAV-mediated truncated dystrophin gene therapy prevented DMD heart disease in neonatal mdx mice and ameliorated heart disease in symptomatic mdx mice. This work represents significant progress towards realization of an effective therapy for DMD heart disease.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.format.extentix, 156 pageseng
dc.identifier.merlinb81633737eng
dc.identifier.oclc706826075eng
dc.identifier.urihttps://hdl.handle.net/10355/10293
dc.identifier.urihttps://doi.org/10.32469/10355/10293eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campuses of the University of Missouri.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.subject.lcshDuchenne muscular dystrophy -- Gene therapyeng
dc.subject.lcshDuchenne muscular dystrophy -- Genetic aspectseng
dc.subject.lcshDuchenne muscular dystrophy -- Animal modelseng
dc.subject.lcshHeart -- Diseases -- Gene therapyeng
dc.subject.lcshHeart -- Diseases -- Genetic aspectseng
dc.subject.lcshDystrophin -- Therapeutic useeng
dc.subject.lcshDystrophin geneseng
dc.subject.lcshParvoviruseseng
dc.subject.lcshTransgenic miceeng
dc.subject.meshMuscular Dystrophy, Duchenne -- therapyeng
dc.subject.meshHeart Diseases -- therapyeng
dc.subject.meshMuscular Dystrophy, Duchenne -- geneticseng
dc.subject.meshMuscular Dystrophy, Duchenne -- complicationseng
dc.subject.meshHeart Diseases -- therapyeng
dc.subject.meshGene Therapy -- methodseng
dc.subject.meshDystrophin -- therapeutic useeng
dc.subject.meshDystrophin -- deficiencyeng
dc.subject.meshDependovirus -- geneticseng
dc.subject.meshMice, Inbred mdxeng
dc.titleDevelopment of gene therapy for Duchenne muscular dystrophy heart disease in the MDX mouse modeleng
dc.typeThesiseng
thesis.degree.disciplineMolecular microbiology and immunology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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