MOUSE MODELING AND ANIMAL DEVELOPMENT

小鼠建模和动物发育

基本信息

批准号：
7916685
负责人：
Natarajan Muthusamy
金额：
$ 24.77万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7916685
关键词：
Animals Antibodies Backcrossings Biological Breeding Cell-Mediated Cytolysis Clinic Clinical Custom Cytokine Signaling Development Disease model Evaluation Funding Gene Targeting Generations Genotype Goals House mice Human Immune Knock-out Knockout Mice Lymphoma Maintenance Mediating Modeling Mus Mutant Strains Mice Natural Immunity Natural Killer Cells Peer Review Pharmacologic Substance Publications Research Research Personnel Resources Roche brand of trastuzumab Role SCID Mice Services Signal Transduction Solid Neoplasm Therapeutic Agents Therapeutic antibodies Transgenic Organisms Treatment Efficacy Xenograft Model Xenograft procedure animal breeding animal resource cancer therapy cost cytokine design improved insight leukemia/lymphoma meetings mouse model mutant novel programs rituximab success therapeutic evaluation tool

项目摘要

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.

核心C（鼠标建模和动物开发核心）将提供全面的支持角色用于生成和维持突变小鼠菌株和疾病模型以评估项目1,2,3和4。定制设计的新型鼠标模型的治疗剂将满足每个项目的具体需求。内部老鼠的模型生成，繁殖和维护将提供最有效的方法，使稀有的突变小鼠应变可供满足本程序应用程序中包含的项目的具体需求。可以访问足够的需要这些专业菌株的数量来维持ppre的种类的显着整合生成研究的临床，临床和生物学项目及时导致。全部四个该计划项目应用程序中的项目利用了各种菌株的普通和/或突变小鼠。转基因和靶向基因的小鼠是该研究计划中的重要工具，小鼠核心是最有效，最具成本效益的方式来提供这些宝贵的动物资源参与协调及时的调查人员。核心一直积极参与一代和新型转基因和基因靶向小鼠模型的表征，这些模型将促进科学目标每个项目。重要的是，需要将几种基因靶向突变菌株回到各种特定项目独特需求的背景。创建了动物育种和维护核心满足每一个的模型生成，购买，维护，繁殖和基因分型的需求项目促进计划项目的整体成功。核心C的具体目标是1）抗体和细胞因子介导的新型转基因和/或敲除小鼠模型的育种治疗评估2）SCID小鼠中HU-PBL异种移植模型的产生先天免疫机制3）集中的小鼠订购，育种，维护和分布 4）每个项目的专门用力服务。核心C的贡献反映在 31个同行在上一个期间使用转基因和/或靶向突变小鼠菌株审查了出版物资金周期。核心C的拟议服务将为治疗功效提供关键见解，机械研究以及改善两种新型抗体介导的细胞细胞毒性的策略有希望的实验小型模块化Irnmuno药物（例如CD37-SMIP）和治疗性目前在诊所中的抗体，例如利妥昔单抗和赫赛汀介导的疗法（项目1,2,4），机制 FCR信号传导（项目1和2），细胞因子信号（项目3和4）和NK细胞发育以及功能（项目3和4）。因此，核心C将构成该计划项目的组成部分在“小鼠 - >人类 - >鼠标 - >人类“翻译研究。