Cell and Animal Model Core

在我们的研究项目中，主要从p53调节因子和效应因子的体外模型中获得的见解导致了对体内验证的迫切需要，并能够使用体内模型获得进一步的理解。在p53范例中正在积极研究的表型不再仅仅是细胞死亡、生长停滞或衰老的问题。相反，体内p53激活的作用可能在不同的细胞和组织类型中具有不同的结果，并且可能在发育阶段方面有所不同。细胞和动物模型核心（核心B）将衍生和维持人和小鼠细胞系以及项目所用冷冻原代细胞的早期传代等分试样的充足储备。它将作为单克隆抗体和经验证的RNAi试剂的储存库。核心还将获得和维持稳定使用的小鼠模型（转基因，敲除等）。以及来自这些小鼠的原代细胞，用于分发给该计划的研究人员。我们的生产和协作计划的研究工作大大受益于体内模型组件，该组件保持小繁殖 我们的研究人员急需的遗传和细胞生物学研究的小鼠品系的殖民地。在隔离墙设施中进行动物研究的高昂费用可通过提供老鼠育种和遗传分析以及共同免疫组织化学方面的共同技术支持而大幅降低。该计划内的几个研究人员和项目共同使用相同的转基因菌株进一步强调了成本效益。最后，该核心将提供组织和/或胚胎准备方面的专业知识和指导，以分析基因表达（蛋白质和mRNA原位）。

Insights gained primarily from in vitro models of p53 regulators and effectors within our research program have led to a critical need for in vivo validation and the ability to gain further understanding using in vivo models. The phenotypes that are actively being examined in the p53 paradigm are no longer simply a matter of cell death, growth arrest or senescence. Instead, the role of p53 activation in vivo will likely have different consequences In different cell and tissue types and will likely differ with regard to developmental stages. The Cell and Animal Model Core (Core B) will derive and maintain human and mouse cell lines as well as adequate stocks of early passage aliquots of frozen primary cells utilized by the projects. It will serve as a repository for monoclonal antibodies and validated RNAi reagents. The Core will also acquire and maintain steadily used mouse models (transgenic, knockouts, etc.) and primary cells derived from these mice for distribution to the investigators in the Program. The research efforts of our productive and collaborative program greatly benefit from an in vivo models component, which maintains small breeding colonies of critically needed mouse strains for genetic and cell biologic investigations by our investigators. The high cost of animal studies in barrier facilities can be reduced substantially by the availability of shared technical support for mouse breeding and genetic analyses and for shared immunohistochemistry. The cost effectiveness is further emphasized by the shared use of the same genetically modified strains by several investigators and projects within the Program. Lastly, the core will provide expertise and guidance in the preparation of tissue and/or embryos for analyses of gene expression (protein and mRNA in situ).