Core A: Experimental Animal Core In exploring this viral model for tumor pathogenesis in the brain, experiments involving animal models are an essential component in all three projects. Thoward this end, the goal of the Experimental Animal Core of this program is to support Projects 1 - 3. In this core, we will focus on the following five goals: (i) Generation and maintenance of JCV T-antigen transgenic mice which spontaneously develop cerebellar medulloblastomas. The mice will be utilized to provide tumor tissue for analysis and for therapeutic treatment as outlined in the individual projects. (ii) Generation and analysis of new lines of transgenic and knockout mice. Inducible JCV T-antigen transgenic will be generated, as well as mice with mutant p53 or beta-catenin. JCV T-antigen transgenic mice will be crossed with mice lacking tumor suppressors such as p53 and Rb family members. (iii) Inoculation of established cell lines along the flanks of Nude mice or syngeneic mice for in vivo evaluation of therapeutic strategies as outlined in Projects 1-3. (iv) Transplantation of established cell lines within the brain parenchyma of Nude or syngeneic mice for in vivo evaluation of therapeutic strategies as outlined in Projects 1-3. (v) Inoculation of either tumor tissue or cell lines along the flanks of Nude mice to evaluate tumorigenecity. Tumor tissue will be excised and passed to Core B for analysis and establishment of cell lines for distribution to Projects 1-3.
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