MOUSE MODELING AND ANIMAL DEVELOPMENT

小鼠建模和动物发育

基本信息

批准号：
8730549
负责人：
Natarajan Muthusamy
金额：
$ 23.99万
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/8730549
关键词：
Animal Model Animals Antibodies B-Cell Lymphomas Backcrossings Biological Breeding Caring Clinical Development Disease Disease model Effector Cell Evaluation Studies Gene Targeting Generations Genetic Engineering Genotype Goals Housing Human Human Herpesvirus 4 Immune Instruction Knock-out Knockout Mice Maintenance Mediating Modeling Monitor Mouse Strains Mus Mutant Strains Mice Myelogenous Natural Immunity Natural Killer Cells Pathogenesis Patients Phenotype Preclinical Testing Program Research Project Grants Research Personnel Resources SCID Mice Services Signal Transduction Solid Neoplasm Staging Suppressor-Effector T-Lymphocytes Therapy Clinical Trials Transgenic Mice Transgenic Organisms Translational Research Travel Treatment Efficacy Validation Xenograft Model Xenograft procedure antibody-dependent cell cytotoxicity cancer therapy cost effective cytokine design drug mechanism in vivo insight leukemia/lymphoma macrophage meetings monocyte mouse model mutant novel pre-clinical programs research clinical testing success therapeutic evaluation

项目摘要

PROJECT SUMMARY (See instructions): Core C (Mouse Modeling and Animal Development Core) will provide comprehensive support for generation and maintenance of wild type and mutant mouse strains and disease models for biological and therapeutic evaluation studies described in Projects 1-4. In-house generation of genetically altered mouse strains allows us to customize the design of mouse models to meet the specific needs of the Projects. Maintenance and breeding services will provide the most efficient and cost effective means of generating, maintaining, and distributing the multiple strains of mice needed for the Projects. The vast majority of our therapeutic trials planned for this P01 application are preceded by preclinical experimentation in mouse models. Thus, timely access to adequate numbers of these specialized strains is needed to adequately service the variety of collaborative pre-clinical projects that are essential for advancement to early stage clinical testing in patients. The core will therefore be 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. The specific aims of the Core C are 1) Breeding and characterization of transgenic or knockout models for antibody and cytokine mediated therapeutic evaluation; 2) Generation of xenograft models including a human-PBL-SCID mouse model with EBV+ B cell lymphoma, syngeneic and xenogeneic models of disseminated leukemia, lymphoma and solid tumors and the generation of conditional knock-out models; 3) Centralized mouse ordering, breeding, maintenance and distribution; 4) Specialized services to each Projects as warranted. The proposed use of mouse models should provide new insights into disease pathogenesis, drug mechanism of action, and therapeutic efficacy of targeted agents for Project 1; in vivo validation of negative regulators of monocyte and macrophage FcyR signaling for Project 2; assessment of NK cell development, tolerance, and function in antibody dependent cellular cytotoxicity in Project 3; and the interaction of myeloid derived suppressor cells with other innate immune effector cells in Project 4. Thus, the Core C will form an integral part of this Program Project Grant by facilitating exploitation of transgenic, knockout, xenograft and other mouse models in translational research.

项目摘要（请参阅说明）：核心C（小鼠建模和动物发育核心）将为野生型和突变小鼠菌株以及疾病模型的生成和维护提供全面的支持，用于项目1-4中描述的生物学和治疗评估研究。内部生成的遗传改变的鼠标菌株使我们能够自定义鼠标模型的设计以满足项目的特定需求。维护和育种服务将提供最有效，最具成本效益的方法，以生成，维护和分发项目所需的多种菌株。我们计划在P01应用计划的绝大多数治疗试验之前是小鼠模型中的临床前实验。因此，需要及时访问足够数量的这些专业菌株，以充分地为临床前项目提供多种协作，这对于进步对患者的早期临床测试至关重要。因此，核心将积极参与新型转基因和基因靶向小鼠模型的产生和表征，这将促进每个项目的科学目标。核心C的具体目的是1）用于抗体和细胞因子介导的治疗评估的转基因或敲除模型的繁殖和表征； 2）生成异种移植模型，包括带有EBV+ B细胞淋巴瘤，散发性白血病，淋巴瘤和实体瘤的人类PBL-SCID小鼠模型，以及有条件敲除模型的产生； 3）集中式小鼠订购，繁殖，维护和分配； 4）为每个项目提供的专业服务。拟议的小鼠模型的使用应提供有关疾病发病机理，作用机理以及项目1的靶向剂的治疗功效的新见解；对项目2的单核细胞和巨噬细胞FCYR信号的负调节剂的体内验证；项目3中NK细胞发育，耐受性和功能的评估；在项目4中，髓样衍生的抑制细胞与其他先天免疫效应细胞的相互作用。因此，核心C将通过促进转化研究中的转基因，敲除，异种移植和其他小鼠模型来形成该程序项目授予的组成部分。