INFLAMMATORY BOWEL DISEASE IN TCR MUTANT MICE

TCR 突变小鼠的炎症性肠病

• 批准号: 2905607
• 负责人: ATUL K BHAN
• 金额: $ 29.57万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-15 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2905607
• 关键词: T cell receptor; animal breeding; animal colony; autoantibody; autoimmune disorder; bactericidal immunity; enteric bacteria; flow cytometry; gene mutation; gene targeting; genetically modified animals; histopathology; immunocytochemistry; inflammatory bowel diseases; laboratory mouse; lymphocyte; site directed mutagenesis; ulcerative colitis

The spontaneous development o chronic colonic inflammation in T cell receptor (TCR) mutant mice, in particular TCRalpha-mutant mice, provides an outstanding animal model of inflammatory bowel disease and a novel model to dissect mucosal immune regulatory mechanisms. The colonic disease in TCRalpha-mutant mice has many features of human ulcerative colitis. Colonies of mice mutant for TCRalpha, TCRbeta, TCRdelta and RAG-1 genes have been developed at the Massachusetts General Hospital. TCRalpha-mutant mice are being crossed with other mutant mice to develop TCRalpha-mutant mice deficient in B cells or a specific cytokine. The studies in these mice will involve characterization of the role of lymphocytes (T and B cell subsets, natural killer cells), antibodies and cytokines in the initiation and perpetuation of colonic inflammation. The studies include histological and immunohistological examination of tissues, flow cytometic and functional characterization of inflammatory cells in the colon, analysis of cytokines in the lymphoid tissues and the colon, detection of autoantibodies and antibacterial immune responses, and cell and serum transfer studies. The project will focus on the hypothesis that cytoline imbalance present at the mucosal site leads to unregulated immune responses to colonic luminal (bacterial) antigens resulting in chronic colonic inflammation. A major aim of the study will be to examine the role of the appendix and luminal bacteria in the development of inflammatory bowel disease. Experiments will also be designed to develop specific interventions in this model of inflammatory bowel disease, which will contribute to the development of new therapeutic modalities for human inflammatory bowel disease.

T细胞中自发发育O慢性结肠炎症 受体（TCR）突变小鼠，特别是tcralpha突变小鼠， 提供了炎症性肠病的出色动物模型 以及一种剖析粘膜免疫调节机制的新型模型。 Tcralpha突变小鼠中的结肠病具有许多特征 人溃疡性结肠炎。 小鼠突变体的菌落，用于tcralpha， TCRBETA，TCRDELTA和RAG-1基因已在 马萨诸塞州综合医院。 tcralpha突变小鼠正在 与其他突变小鼠交叉以形成tcralpha突变小鼠 缺乏B细胞或特定细胞因子。 这些小鼠的研究 将涉及表征淋巴细胞的作用（T和B细胞 子集，天然杀伤细胞），抗体和细胞因子的开始 和结肠炎症的永久性。 研究包括 组织学和免疫组织学检查，流量 在 结肠，淋巴组织和结肠中细胞因子的分析， 检测自身抗体和抗菌免疫反应，以及 细胞和血清转移研究。 该项目将重点放在 假设粘膜部位存在的细胞酚不平衡导致 对结肠腔（细菌）抗原的不受调节的免疫反应 导致慢性结肠炎症。 研究的主要目的 将检查附录和腔细菌在 炎症性肠病的发展。 实验也将是 旨在在此模型中制定特定干预措施 炎症性肠病将有助于发育 人类炎症性肠病的新治疗方式。