Animal Modeling Core

动物建模核心

• 批准号: 10415108
• 负责人: ANDRZEJ A. DLUGOSZ
• 金额: $ 27.49万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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/10415108
• 关键词: 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; 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; base; cell immortalization; conditional mutant; cost; design; human model; in vivo; insight; interest; member; mouse model; multiple omics; novel; preclinical study; response; screening; skin disorder; tissue processing; tool; ultraviolet irradiation

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.

对于集中式核心，提供专门针对鼠标的专业知识和培训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年的密集鼠标建模 核心主任和副主任的专业知识，动物模型核心（AMC）的大学 密歇根皮肤生物学和疾病资源中心（UM-SBDRC）将作为一个共享资源， 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。核心小组还将提供必要的技术专门知识和指导， 进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 所有调查人员独立获得所需知识和专业知识的效率低下， 成功地设计和实施这些研究。因此，本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， 并为有兴趣在小鼠中进行皮肤相关研究的中心成员进行故障排除。我们将提供 通过以下服务和培训提供实际帮助。1)设计和开发咨询 项目特异性GEMM，包括常规的，Cre诱导的，多西环素诱导的和条件性的 突变小鼠2)小鼠模型的生产和验证指南，包括转基因构建， 验证、基因分型和GEMM生产;筛选;育种、菌株建立和验证。3)在 体内操作，包括转基因诱导方案，UV照射，通过 外源性药物、博来霉素诱导的纤维化和原位异种移植物和同种异体移植物。4)GEMM 表型分型，包括适当的组织收集和处理;形态学、生物化学和分子生物学 表征;跨种属验证;以及GEMM衍生原代培养物的建立， 考虑到关键的实验变量，包括身体部位，性别， 年龄在本核心的协助下进行的工作将：1）极大地促进 中心成员通过在以下领域的工作确定了关键炎症介质和相互作用途径： 功能分析核心; 2）确保整个范围内一致和可重复的表型表征 3）产生新的人类皮肤病小鼠模型， 对皮肤研究界的价值; 4）促进新的小鼠建模技术的发展， 将用于多学科;和5）提供强大的GEMM和组织详细的多组学 Functional Analytics Core中的分析。