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.

对集中核心的核心需求未满足，以提供专业知识和专门针对鼠标的培训与皮肤生物学和疾病有关的模型。利用超过18年的密集型鼠标建模核心主任兼副主任，动物建模核心（AMC）的专业知识密歇根州皮肤生物学和疾病基于资源的中心（UM-SBDRC）将作为共享资源促进小鼠模型的设计，开发和表征，旨在获得更深入的了解皮肤生物学和疾病。核心还将提供适当的技术专长和指导执行各种体内程序和测定。常规和诱导的遗传工程小鼠模型（GEMM）为功能分析和临床前研究提供了强大的工具，但这是昂贵的效率低下，所有调查人员都无法独立获取所需的知识和专业知识成功设计并进行这些研究。因此，该核心的总体长期目标是促进最先进的鼠标模型的开发和使用，并提供相关的咨询，培训，并对有兴趣在小鼠中进行皮肤相关的研究的中心成员进行故障排除。我们将提供动手协助以下服务和培训。 1）有关设计和开发的咨询特定项目的宝石，包括常规，可诱导，强力霉素诱导和条件突变小鼠。 2）生产和验证鼠标模型的指南，包括转基因结构，验证，基因分型和GEMM生产；筛选；育种，应变建立和验证。 3）in 体内操作，包括转基因诱导方案，紫外线照射，通过外源性剂，博来霉素诱导的纤维化，原位异种移植物和同种异体移植物。 4）宝石表型，包括适当的组织收集和加工；形态学，生化和分子表征；跨物种验证；以及建立杰明衍生的原始文化和永生的细胞系，考虑到关键的实验变量，包括身体部位，性别和年龄。在此核心的协助下执行的工作1）极大地促进了体内的功能验证中心成员通过在功能分析核心； 2）确保整个范围内的一致和可重现的表型表征中心成员使用的鼠标模型； 3）产生新型的人类皮肤疾病的老鼠模型对皮肤研究社区的价值； 4）促进新的鼠标建模技术的发展将用于多个学科； 5）提供有力的宝石和组织，用于详细的多摩斯功能分析核心中的分析。