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dc.contributor.advisorBryda, Elizabeth C.eng
dc.contributor.authorHanson, Marina McCoy, 1984-eng
dc.date.issued2016eng
dc.date.submitted2016 Falleng
dc.descriptionAbstract from short.pdf.eng
dc.descriptionDissertation supervisor: Dr. Elizabeth C. Bryda.eng
dc.descriptionIncludes vita.eng
dc.description.abstractCurrent methodologies of cell ablation have limitations with respect to the types of cells that can be targeted, the lack of specificity of ablation and the lack of appropriate methodologies to facilitate their use across species. The goal of our study is to provide proof of concept that intermedilysin (ILY) administration to ablate cells expressing human CD59 (hCD59) provides a sensitive, specific, and versatile tool for cell ablation in rats and zebrafish. While effective cell ablation using this system has been demonstrated previously in mice, it has not been tested in other model organisms. We generated a new transgenic rat line to study hemolytic anemia which expresses hCD59 specifically on erythrocytes rendering them susceptible to lysis by administration of the otherwise inert bacterial toxin, ILY. ILY intravenous injection dramatically reduced hematocrit within 10 minutes, with no effect on wild type rats. To test ablation of cell types within whole organs, we have generated a fluorescent protein-tagged hCD59 which can be expressed constitutively in multiple cell types, including tyronsine-hydroxylase (TH)-expressing neurons, when Cre recombinase is present. Such models can be useful for study of neurodegenerative disorders, such as Parkinson's disease. When rats were dosed with ILY, there was a decrease in TH-positive neurons. To demonstrate applicability in non-rodent models, we are testing the efficacy of the hCD59-ILY system in zebrafish. Ongoing studies aim to validate the hCD59-ILY system by production of transgenic zebrafish which express hCD59 in motor neurons. The use of hCD59-ILY will have wide application for any studies in any species that can benefit from selective cell ablation in vivo.eng
dc.description.bibrefIncludes bibliographical references (pages 111-132).eng
dc.format.extent1 online resource (vi, 133 pages) : illustrationseng
dc.identifier.merlinb118801259eng
dc.identifier.oclc988582532eng
dc.identifier.urihttps://hdl.handle.net/10355/59849
dc.identifier.urihttps://doi.org/10.32469/10355/59849eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccesseng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.eng
dc.subject.FASTStreptolysineng
dc.subject.FASTCell-mediated cytotoxicityeng
dc.subject.FASTHemolysis and hemolysinseng
dc.subject.FASTAnimal models in researcheng
dc.titleIntermedilysin-mediated cell ablation in the rat and zebrafisheng
dc.typeThesiseng
thesis.degree.disciplineVeterinary pathobiology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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