MOUSE MODELING AND ANIMAL DEVELOPMENT

核心C（小鼠建模和动物开发核心）将提供全面的支持作用 用于产生和维持突变小鼠品系和疾病模型， 项目1、2、3和4所述的治疗剂。定制设计的新型小鼠模型的生成 将满足每个项目的具体需求。内部小鼠模型生成、育种和 维护将提供最有效的手段，使罕见的突变小鼠品系，以满足 本计划应用程序中包含的项目的具体需求。随时可获得充足的 需要大量的这些特化菌株来维持各种前- 临床、临床和生物学项目，以便及时产生研究成果。所有四 本计划项目申请中的项目利用各种品系的正常和/或突变小鼠。 转基因和基因靶向小鼠是这项研究计划的重要工具，小鼠核心是 最有效和最具成本效益的方式来提供这些宝贵的动物资源的数量 调查人员及时协调。核心一直积极参与生成和 表征新型转基因和基因靶向小鼠模型，这将有助于实现以下科学目标： 每个项目。重要的是，需要将几种基因靶向突变株回交到各种突变株上。 满足特定项目的独特需求。动物饲养和维护核心是创建 为了满足每一个人的模型生成、购买、维护、育种和基因分型的需要， 项目，以促进项目的整体成功。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/或敲除小鼠模型的培育 2）在SCID小鼠中产生hu-PBL异种移植物模型以研究人 先天免疫机制3）集中的小鼠排序、繁殖、维持和分布 4)为每个项目提供基于需求的专业服务。核心C的贡献体现在 31篇同行评审的出版物使用转基因和/或靶向突变小鼠品系， 融资周期。核心C的拟议服务将提供对治疗效果的关键见解， 机制研究和策略，以提高抗体介导的细胞毒性的两种新的 有前途的实验性小模块免疫药物，如CD 37-SMIP）和治疗性药物 目前在临床上使用的抗体如利妥昔单抗和赫赛汀介导的治疗（项目1、2、4）， FcR信号传导（项目1和2），细胞因子信号传导（项目3和4）和NK细胞发育， 功能（项目3和4）。因此，Core C将成为本项目不可分割的一部分， 促进了在“小鼠”中开发转基因、敲除和hu-PBL异种移植小鼠模型， >人类->小鼠->人类”的实验研究。

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.