Animal Modeling Core

对提供专门针对鼠标的专业知识和培训的集中式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18年来密集的鼠标建模 芝加哥大学动物建模核心中心(AMC)核心主任和副主任的专业知识 密歇根皮肤生物学和疾病资源中心(UM-SBDRC)将作为共享资源 促进鼠标模型的设计、开发和表征，旨在更深入地了解 皮肤生物学和疾病。核心还将提供必要的技术专业知识和指导，以适当 进行各种活体程序和分析。常规可诱导的基因工程小鼠 模型(GEM)为功能分析和临床前研究提供了强大的工具，但成本高昂 以及所有调查人员独立获取所需的知识和专业知识的效率低下 成功地设计和实施了这些研究。因此，这一核心的总体、长期目标是 促进最先进的鼠标模型的开发和使用，并提供相关咨询、培训、 和故障排除中心成员对在老鼠身上进行皮肤相关研究感兴趣。我们将提供 通过以下服务和培训提供实践援助。1)设计开发咨询 项目特定的GEMM，包括常规的、Cre诱导的、多西环素诱导的和有条件的 突变的小鼠。2)生产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、紫外线照射、通过以下方式诱导皮肤炎症 外源性药物，博莱霉素诱导的纤维化，以及原位异种移植和同种异体移植。4)GEMM 表型鉴定，包括适当的组织收集和加工；形态、生化和分子 鉴定；跨物种验证；以及建立来自GEMM的原代培养和 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极大地促进体内、功能验证 关键炎症介质和相互作用途径由中心成员通过在 功能分析核心；2)确保整个范围内一致且可重现的表型特征 中心成员使用的小鼠模型；3)产生新的人类皮肤病小鼠模型 对皮肤研究界的价值；4)推动新的鼠标建模技术的发展， 将用于多个学科；以及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。

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.