MOUSE MODELING AND ANIMAL DEVELOPMENT

核心C(老鼠建模和动物发展核心)将提供全面的支持作用 用于产生和维护突变小鼠品系和疾病模型以评估 项目1、2、3和4中描述的治疗剂：定制设计的新一代小鼠模型 将满足每个项目的具体需求。室内小鼠模型的生成、繁育和 维护将提供最有效的手段，使罕见的突变小鼠品系可用于满足 本计划申请中所包含的项目的具体需求。随时可以访问足够的 需要大量的这些专门的菌株来维持各种前病毒的显著整合 临床、临床和生物项目研究成果的及时产生。四个都是 本项目中的项目申请利用了各种品系的正常和/或突变小鼠。 转基因和以基因为靶标的小鼠是这个研究计划中的基本工具，而小鼠的核心是 以最有效和最具成本效益的方式向数量众多的 调查人员以协调及时的方式参与其中。核心一直积极参与发电和 新的转基因和基因靶向小鼠模型的特征将促进科学目标 每一个项目。重要的是，几个以基因为靶标的突变菌株需要回交到不同的 具体项目的独特需求的背景。创建了动物繁育和维护核心 为了满足模型生成、购买、维护、育种和基因分型的需要， 促进计划项目全面成功的项目。核心C的具体目标将是1) 抗体和细胞因子介导的新型转基因和/或基因敲除小鼠模型的培育 疗效评价2)人外周血淋巴细胞SCID小鼠移植模型的建立 先天免疫机制3)小鼠的集中订购、选育、维护和分配 4)为每个项目提供所需的专门服务。核心C的贡献体现在 在过去的一年中，使用转基因和/或靶向突变小鼠品系的31篇同行评议的文章 资金周期。拟议的核心C服务将提供对治疗效果的关键见解， 机制研究，以及提高抗体介导的细胞毒性的策略 有前途的实验性小模块免疫药物(如CD37-SMIP)和治疗 目前临床上的抗体，如利妥昔单抗和赫赛汀介导的治疗(项目1，2，4)，机制 FCR信号(项目1和2)、细胞因子信号(项目3和4)和NK细胞发育和 功能(项目3和项目4)。因此，核心C将通过以下方式形成该计划项目的组成部分 促进转基因、基因敲除和hU-PBL异种移植小鼠模型的开发 &gt；人-&gt；鼠标-&gt；人“翻译研究。

The Core C (Mouse modeling and animal development core) will provide a comprehensive supportive role for generation and maintenance of mutant mouse strains and disease models for the evaluation of the therapeutic agents described in projects 1,2,3and 4. Custom designed generation of novel mouse models will meet the specific needs of each of the projects. In-house mouse model generation, breeding and maintenance will provide the most efficient means of making the rare mutant mouse strains available to meet the specific needs of the projects contained within this program application. Ready access to adequate numbers of these specialized strains is needed to maintain the significant integration of the variety ofpre- clinical, clinical and biological projects for the generation of research results in a timely fashion. All four projects in this program project application make use of normal and/or mutant mice of various strains. Transgenic and gene-targeted mice are essential tools in this research program, and a mouse core is the most efficient and cost-effective way to supply these invaluable animal resources to the number of investigators involved in a coordinated timely fashion. The core has been actively involved in generation and characterization of novel transgenic and gene targeted mouse models that will facilitate the scientific goals of each of the projects. Importantly, several gene targeted mutant strains need to be backcrossed onto various backgrounds for the unique needs of specific projects. The animal breeding and maintenance core is created to satisfy the needs for model generation, purchase, maintenance, breeding, and genotyping for each of the projects to facilitate overall success of the program project. The specific goals of the Core C will be 1) Breeding of novel transgenic and/or knockout mouse models for antibody and cytokine mediated therapeutic evaluation 2) Generation of hu-PBL xenograft models in SCID mice to study human innate immune mechanisms 3) Centralized mouse ordering, breeding, maintenance and distribution 4)Specialized needbasedservices to each of the projects. The contribution of the Core C is reflected in the 31 peer reviewed publications using transgenic and/or targeted mutant mouse strains during the previous funding cycle. The proposed services of the Core C will provide critical insights into therapeutic efficacy, mechanistic studies, and strategies to improve antibody mediated cellular cytotoxicity of both novel promising experimental small modular irnmuno Pharmaceuticals such as CD37-SMIP) and therapeutic antibodies currently in clinic such as Rituximab and Herceptin mediated therapy (Project 1,2,4), mechanisms of FcR signaling (Projects 1 and 2), cytokine signaling (Project 3 and 4) and NK cell development and function (Project 3 and 4). Thus the Core C will form an integral part of this program project by facilitating exploitation of transgenic, knockout and hu-PBL xenograft mouse models in "Mouse- >human -> Mouse->human" translationalresearch.