Development of Mice with Conditional ICAM-1 Deletion

研究资源的产生旨在揭示胰岛β细胞与免疫系统相互作用的新机制，对于理解自身免疫性疾病的发生和进展，加强药物开发策略和其他治疗努力的进展至关重要。细胞内粘附分子-1 （ICAM-1）是1型糖尿病（T1D）发展的关键组成部分，但由于缺乏可用和适当的模型系统，该蛋白的组织特异性贡献尚未得到研究。在此，我们概述了在C57BL/6和非肥胖糖尿病（NOD）背景下制造ICAM-1条件缺失转基因小鼠的策略。这个R03项目将产生两个新的和重要的小鼠系，用于探索T1D自身免疫发病和进展的基本机制，重要的是，提供免疫细胞如何破坏胰岛β细胞的见解。这些新的小鼠品系将有可能测试只有组织特异性基因缺失才能想象到的创新假设，为调节自身免疫、胰岛炎症、组织移植排斥、血管化事件和T1D发病提供重要的机制见解。我们预计该方法可广泛应用于具有自身免疫和自身炎症成分的其他疾病的研究，以及ICAM-1蛋白生物学的一般研究。

The generation of research resources designed to uncover novel mechanisms of islet beta-cell interaction with the immune system are vitally important for progress in understanding autoimmune disease onset and progression, enhancing drug development strategies, and other curative endeavors. Intracellular adhesion molecule-1 (ICAM-1) is a critical component in the development of type 1 diabetes (T1D) but the tissue-specific contributions of this protein have not been examined due to lack of available and appropriate model systems. Herein, we outline a strategy to make transgenic mice with conditional deletion of ICAM-1 on both the C57BL/6 and non-obese diabetic (NOD) backgrounds. This R03 project will generate two novel and important mouse lines with which to probe basic mechanisms underlying autoimmune onset and progression of T1D, and importantly, provide insights into how immune cells destroy islet beta cells. These new mouse lines will make it possible to test innovative hypotheses only conceivable with tissue-specific gene deletions, providing important mechanistic insights into events regulating autoimmunity, pancreatic islet inflammation, tissue graft rejection, vascularization events, and T1D onset. We anticipate broad applicability to studies of other diseases with autoimmune and auto-inflammatory components and for general studies on the biology of the ICAM-1 protein.