Animal Modeling Core

动物建模核心

基本信息

批准号：
10643966
负责人：
ANDRZEJ A. DLUGOSZ
金额：
$ 26.84万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10643966
关键词：
Acceleration Age Allografting Animal Model Biochemical Biological Assay Biology Bleomycin Breeding Cell Line Collection Communities Consultations Cutaneous Development Discipline Disease Doxycycline Embryo Ensure Fibrosis Gender Genetically Engineered Mouse Genotype Goals Inflammation Inflammation Mediators Knowledge acquisition Michigan Molecular Morphology Mus Mutant Strains Mice Pathologic Pathway interactions Phenotype Procedures Production Protocols documentation Reproducibility Reproducibility of Results Research Research Personnel Resource Sharing Resources Services Site Skin Standardization Technical Expertise Technology Tissue Banks Tissue Sample Tissues Training Transgenes Transgenic Mice Universities Validation Work Xenograft procedure cell immortalization conditional mutant cost design gene induction human model in vivo inducible Cre insight interest member mouse model multiple omics novel preclinical study response screening skin disorder tissue processing tool ultraviolet irradiation

项目摘要

There is an unmet need for a centralized Core providing expertise and training specifically focused on mouse models relevant to cutaneous biology and disease. Capitalizing on over 18 years of intensive mouse modeling expertise by the Core Director and Associate Director, the Animal Modeling Core (AMC) of the University of Michigan Skin Biology and Diseases Resource-based Center (UM-SBDRC) will serve as a shared resource to facilitate the design, development, and characterization of mouse models aimed at gaining deeper insight into skin biology and disease. The Core will also provide technical expertise and guidance needed to properly perform a variety of in vivo procedures and assays. Conventional and inducible genetically-engineered mouse models (GEMMs) provide powerful tools for functional analyses and preclinical studies, but it would be costly and inefficient for all investigators to independently acquire the knowledge and expertise needed to successfully design and carry out these studies. Thus, the overarching, long-term goal of this Core is to facilitate the development and use of state-of-the-art mouse models and provide relevant consultation, training, and troubleshooting for Center members interested in pursuing skin-related studies in mice. We will provide hands-on assistance with the following services and training. 1) Consultation on the design and development of project-specific GEMMs, including conventional, Cre-inducible, doxycycline-inducible, and conditional mutant mice. 2) Guidance for producing and validating mouse models, including transgene construction, verification, genotyping, and GEMM production; screening; breeding, strain establishment, and validation. 3) In vivo manipulation, including transgene induction protocols, UV irradiation, induction of skin inflammation by exogenous agents, bleomycin-induced fibrosis, and orthotopic xenografts and allografts. 4) GEMM phenotyping, including proper tissue collection and processing; morphologic, biochemical, and molecular characterization; cross-species validation; and establishment of GEMM-derived primary cultures and immortalized cell lines, taking into consideration key experimental variables including body site, gender, and age. Work performed with the assistance of this Core will 1) greatly facilitate the in vivo, functional validation of key inflammatory mediators and interacting pathways identified by Center Members through work done in the Functional Analytics Core; 2) ensure consistent and reproducible phenotype characterization across the range of mouse models used by Center Members; 3) yield novel mouse models of human skin disease that will be of value to the skin research community; 4) promote the development of new mouse modeling technology that will be of use to multiple disciplines; and 5) provide powerful GEMMs and tissues for detailed multi-omics analysis in the Functional Analytics Core.

对于提供专门针对鼠标的专业知识和培训的集中核心的需求尚未得到满足与皮肤生物学和疾病相关的模型。利用超过 18 年的密集小鼠建模经验由澳大利亚大学动物模型核心 (AMC) 核心主任和副主任提供的专业知识密歇根皮肤生物学和疾病资源中心 (UM-SBDRC) 将作为共享资源促进小鼠模型的设计、开发和表征，旨在更深入地了解皮肤生物学和疾病。核心还将提供适当的技术专业知识和指导执行各种体内程序和测定。常规和诱导型基因工程小鼠模型（GEMM）为功能分析和临床前研究提供了强大的工具，但成本高昂所有研究人员独立获取所需的知识和专业知识的效率低下成功地设计并进行了这些研究。因此，该核心的总体长期目标是促进最先进的小鼠模型的开发和使用，并提供相关咨询、培训、并为有兴趣进行小鼠皮肤相关研究的中心成员提供疑难解答。我们将提供提供以下服务和培训的实际帮助。 1）设计开发咨询项目特定的 GEMM，包括传统的、Cre 诱导的、多西环素诱导的和条件的突变小鼠。 2) 制作和验证小鼠模型的指南，包括转基因构建，验证、基因分型和 GEMM 生产；筛查；育种、菌株建立和验证。 3）在体内操作，包括转基因诱导方案、紫外线照射、通过诱导皮肤炎症外源性药物、博莱霉素诱导的纤维化以及原位异种移植物和同种异体移植物。 4）GEMM 表型分析，包括适当的组织收集和处理；形态学、生物化学和分子学表征；跨物种验证；以及 GEMM 衍生的原代培养物的建立和永生化细胞系，考虑到关键的实验变量，包括身体部位、性别和年龄。在此核心的协助下进行的工作将 1) 极大地促进体内功能验证中心成员通过在以下领域所做的工作确定了关键的炎症介质和相互作用途径功能分析核心； 2) 确保整个范围内表型表征的一致性和可重复性中心成员使用的小鼠模型； 3）产生人类皮肤病的新型小鼠模型对皮肤研究界的价值； 4）促进新型小鼠建模技术的发展将适用于多个学科； 5) 为详细的多组学提供强大的 GEMM 和组织功能分析核心中的分析。