CORE--EXPERIMENTAL ANIMAL

核心A：实验动物核心 在探索这种用于脑肿瘤发病机制的病毒模型时，涉及动物模型的实验是所有三个项目的重要组成部分。为此，该项目的实验动物核心的目标是支持项目1 - 3。在这一核心中，我们将重点实现以下五个目标： (i)自发发展小脑髓母细胞瘤的JCV T抗原转基因小鼠的产生和维持。小鼠将用于提供肿瘤组织，用于分析和治疗，如个别项目所述。 (ii)转基因和基因敲除小鼠新品系的产生和分析。将产生可诱导的JCV T抗原转基因小鼠，以及具有突变型p53或β-连环蛋白的小鼠。JCV T抗原转基因小鼠将与缺乏肿瘤抑制因子如p53和Rb家族成员的小鼠杂交。 (iii)沿着裸小鼠或同系小鼠的侧腹接种已建立的细胞系，用于项目1-3中概述的治疗策略的体内评价。 (iv)在裸鼠或同基因小鼠脑实质内移植已建立的细胞系，用于项目1-3中概述的治疗策略的体内评价。 (v)沿裸鼠侧腹沿着接种肿瘤组织或细胞系，以评价致瘤性。 将切除肿瘤组织并转移至核心B进行分析，并建立细胞系，以分配至项目1-3。

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.