Cellular and Transgenic Phenotyping Core

细胞和转基因表型核心将提供一个面向服务的资源沿着正在进行的 技术开发和优化，确保项目的效率和生产力 候选胰腺癌序列的功能评价的研究者。这将是 通过集中和标准化使用体外、基于细胞的测定以及 详细评估小鼠、斑马鱼和异种移植模型中的体内表型。老鼠是一个很好的- 特征的哺乳动物模型系统与广泛的遗传工具箱可用于遗传 操作以产生原位肿瘤，免疫缺陷菌株，其促进直接体内 分析人类癌细胞作为异种移植物，以及与人类癌症生物学相关的跟踪记录， 治疗学斑马鱼是一种新兴的癌症遗传学模型和发育模型， 高效，允许高通量的体内脊椎动物遗传筛选，并且由于 它们成熟时的小尺寸和发育期间的光学清晰度。核心A将提供集中服务， 根据标准化标准有效使用和组织学分析这些模型。具体 目的：1）提供组织病理学解释，组织增殖分析，和基因 项目1、2、3和4提供的小鼠和斑马鱼组织的途径评价;以及目标2）应用 并在免疫缺陷小鼠中改进异位和原位异种移植模型，用于体内评价 包括基因或微小RNA序列在内的候选胰腺癌序列的功能 项目2、3和4的致瘤性、肿瘤生长、基质发育和转移测定。 相关性（参见说明）： 胰腺癌相关基因和microRNA的功能特征将导致 发现了迫切需要的治疗胰腺癌的新靶点。斑马鱼 本提案中描述的小鼠模型在未来也将作为验证的理想工具， 在将新疗法投入人体临床试验之前，对这些新疗法进行安全性测试。

The Cellular and Transgenic Phenotyping Core will provide a service-oriented resource along with ongoing technique development and optimization that will ensure the efficiency and productivity of project investigators in the functional evaluation of candidate pancreatic cancer sequences. This will be accomplished through the centralized and standardized use of both in vitro, cell based assays as well as detailed assessment of in vivo phenotypes in mouse, zebrafish, and xenograft models. The mouse is a well- characterized mammalian model system with an extensive genetic toolbox available for genetic manipulations to generate autochthonous tumors, immunodeficient strains that facilitate direct in vivo analysis of human cancer cells as xenografts, and a track record of relevance to human cancer biology and therapeutics. Zebrafish are an emerging cancer genetics model and developmental model that arecost efficient, permit high throughput in vivo vertebrate genetic screens, and can be efficiently analyzed due to their small size at maturity and optical clarity during development. Core A will provide centralized services for the efficient use and histological analysis of these models according to standardized criteria. The Specific Aims are: Aim 1) to provide histopathology interpretation, histological proliferation analysis, and gene pathway evaluation of mouse and zebrafish tissues supplied by Projects 1,2,3, and 4; and Aim 2) to apply and refine ectopic and orthotopic xenograft models in immunodeficient mice for in vivo evaluation of the function of candidate pancreatic cancer sequences including genes or microRNA sequences using in vivo tumorigenicity, tumor growth, stromal development, and metastasis assays for Projects 2,3, and 4. RELEVANCE (Seeinstructions): Functional characterizationof the genes and microRNA'sinvolved in pancreatic cancer will lead to the discovery of new targets for treatment of pancreatic cancer which are desperately needed. The zebrafish and mouse models characterized in this proposal will in the future also serve as ideal tools for validation and safety testing of these new treatments before moving the new therapies into human clinical trials.