Autoimmune Mouse Core

该计划资助包括四个综合项目：项目1（PI Jenkins）体内外周耐受性分析，以使用MHC II四聚体试剂识别糖尿病患者和糖尿病小鼠的自身反应性CD 4 + T细胞，项目2（PI Mueller）无反应性T细胞的功能表征。项目3（PI Hogquist）使用新型小鼠报告基因定义健康和疾病中多克隆群体的自身反应性，项目4（PI Mescher）研究CD 8 + T细胞和关键第三信号细胞因子在1型糖尿病起始期间的作用。每个项目都需要特定的小鼠品系，四个核心中的三个需要自发的糖尿病监测，病理分析和与糖尿病特别相关的动物护理。该分析将包括通过标准H&E进行的胰岛炎，以及先进技术的辅助，包括特定细胞类型的免疫荧光，以及胰腺和胰腺淋巴结的流式细胞术。该核心非常适合进行这些研究，因为Fife博士已经使用相同的技术和类似的分析超过11年（1-8）。 自身免疫小鼠核心的主要作用包括： A）提供成本有效的动物护理和NOD、B6.g7和在NOD背景上的遗传敲除和转基因系的育种，用于自身免疫实验。自发性糖尿病的发展使常规育种复杂化，需要额外的关注以及群体整合，以最大限度地减少冗余和动物成本。 B）提供核心小鼠的糖尿病监测和糖尿病管理。必要时，将为核心饲养的糖尿病小鼠品系提供常规自发糖尿病筛查和胰岛素治疗。差异基因敲除或转基因小鼠可加速糖尿病，因此可能需要专门护理。为了产生足够数量的定时糖尿病小鼠，必须维持和协调大的队列以提供足够和一致的实验小鼠。 C）提供糖尿病监测、治疗和实验小鼠的组织收获。核心将监控

This program grant consists of four integrated projects: Project 1 (PI Jenkins) Analysis of peripheral tolerance in vivo to identify autoreactive CD4+ T cells from diabetic human patients and diabetic mice using MHC II tetramer reagents, Project 2 (PI Mueller) Functional characterization of anergic T cells. Project 3 (PI Hogquist) to define the self-reactivity of polyclonal populations in health and disease using a novel mouse reporter, and Project 4 (PI Mescher) to investigate the role for CD8+ T cells and critical third signal cytokines during the initiation of type 1 diabetes. Each project requires specific mouse lines and three of the four cores require spontaneous diabetes monitoring, pathological analysis and animal care specifically relevant for diabetes. This analysis will consist of insulitis by standard H&E, and assistance with advanced techniques including immunofluorescence of specific cell types, and flow cytometry from pancreas and pancreatic lymph nodes. This core is ideally suited to conduct these studies because identical techniques and similar analysis have been carried out for >11 years by Dr. Fife (1-8). The principle roles ofthe Autoimmune Mouse Core include: A) Provide cost effective animal care and breeding of NOD, B6.g7 and genetic knockout and transgenic lines on the NOD background for autoimmune experimentation. Development of spontaneous diabetes complicates routine breeding and requires additional attention as well as colony consolidation minimizes redundancy and animal costs. B) Provide diabetes monitoring and diabetes management of core mice. Routine spontaneous diabetes screening and insulin therapy will be provided as necessary for diabetic mouse strains being maintained by the core. Differential genetic knockout or transgenic mice can accelerate diabetes and therefore specialized care may be required. In order to generate sufficient numbers of timed diabetic mice, large cohorts must be maintained and coordinated to provide sufficient and consistent experimental mice. C) Provide diabetes monitoring, treatment, and tissue harvesting of experimental mice. The core will monito