Autoimmune Mouse Core

自身免疫鼠标核心

基本信息

批准号：
8841658
负责人：
Brian T Fife
金额：
$ 13.52万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8841658
关键词：
Animals Attention Autoimmune Process Autoimmunity Basic Science Blood Glucose Breeding CD4 Positive T Lymphocytes CD8B1 gene Caring Cytokine Signaling Development Diabetes Mellitus Diabetic mouse Disease Flow Cytometry Genetic Goals Grant Health Hematoxylin and Eosin Staining Method Human Immunofluorescence Immunologic Inbred NOD Mice Instruction Insulin Insulin-Dependent Diabetes Mellitus Islets of Langerhans Knock-out Knockout Mice Leucocytic infiltrate Monitor Mononuclear Mouse Strains Mus Output Pancreas Pathogenesis Patients Peripheral Population Reagent Reporter Research Research Personnel Role Services Staining method Stains T-Lymphocyte Techniques Time Tissue Harvesting Tissues Training Transgenic Mice Transgenic Organisms Translational Research Urine animal breeding animal care base cell type central tolerance cohort cost cost effective design diabetes management diabetic experience in vivo lymph nodes mouse model non-diabetic novel peripheral tolerance programs screening transgene expression wasting

项目摘要

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

该计划拨款由四个综合项目组成：项目 1 (PI Jenkins) 使用 MHC II 四聚体试剂分析体内外周耐受性，以识别糖尿病患者和糖尿病小鼠的自身反应性 CD4+ T 细胞，项目 2 (PI Mueller) 无能细胞的功能表征T细胞。项目 3 (PI Hogquist) 使用新型小鼠报告基因定义多克隆群体在健康和疾病中的自身反应性，项目 4 (PI Mescher) 研究 CD8+ T 细胞和关键的第三信号细胞因子在类型启动过程中的作用1 糖尿病。每个项目都需要特定的小鼠品系，四个核心中的三个需要与糖尿病特别相关的自发糖尿病监测、病理分析和动物护理。该分析将包括标准 H&E 的胰岛炎分析，以及先进技术的协助，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 (1-8) 已使用相同的技术和类似的分析超过 11 年。自身免疫鼠标核心的主要作用包括： A) 为自身免疫实验提供具有成本效益的动物护理和 NOD、B6.g7 以及 NOD 背景上的基因敲除和转基因品系的育种。自发性糖尿病的发生使常规饲养变得复杂，需要额外的关注，并且群体整合可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。对于核心维持的糖尿病小鼠品系，将根据需要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会加速糖尿病，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，必须维持和协调大型群体以提供足够且一致的实验小鼠。 C) 提供实验小鼠的糖尿病监测、治疗和组织采集。核心将监控