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dc.contributor.authorPantginis, Joseph
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 59-06, Section: B, page: 2592.;Advisors: Jack Lenz.
dc.description.abstractFeline leukemia virus (FeLV) is an important pathogen of domestic cats. It causes a wide range of neoplastic, degenerative, and proliferative diseases. I designed and employed a novel genetic system to identify genetic determinants of pathogenicity of FeLV in a mouse system. The reason for this is that feline T cell lymphomas have a latent period of several years. A recombinant virus was generated that contained the U3 region of a naturally occurring FeLV isolate, LC-FeLV, linked to the remainder of the genome of the MuLV SL3. When inoculated into AKR/J mice, the recombinant virus induced T-cell lymphomas nearly as quickly as SL3 with 100% efficiency. In transcriptional assays, the U3 sequences of LC-FeLV were found to exhibit 50-80% the transcriptional activity as the corresponding sequences of SL3 in various T lymphocyte lines. I concluded that the FeLV LTR contains a potent genetic determinant of T-cell lymphomagenicity. The next goal was to identify specific regions within the FeLV LTR U3 that are critical for lymphomagenesis. The sites chosen for mutation were the sites that bind the factors Myb, Ets, CBF, and the E-Box family of transcription factors. The Myb and CBF site mutations greatly inhibit transcriptional activation. The Ets and E-Box mutations affect transcription only to a lesser extent. In pathogenesis experiments, the CBF mutation caused diseased with 100% efficiency just as fast as the wild type. The Myb mutation also caused 100% incidence of disease but with approximately double the latent period equal to the time of the Ets and E-Box viruses. Reversion analysis identified a single base pair mutation within the CBF and Myb mutants. This point mutation was tested in transcriptional assays and was shown to be at least in part acting as a suppressor mutation which would account for the level of pathogenesis seen for the Myb and CBF mutants.
dc.publisherProQuest Dissertations & Theses
dc.subjectMolecular biology.
dc.subjectAnimal diseases.
dc.titleFeline leukemia virus pathogenesis and regulation: A model system for lymphomagenesis

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