Autoreactive T Cells in NOD TCR Transgenic Mice

NOD TCR 转基因小鼠中的自身反应性 T 细胞

• 批准号: 6680523
• 负责人: KATHRYN M HASKINS
• 金额: $ 20.8万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2005-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6680523
• 关键词: NOD mouse; T cell receptor; T lymphocyte; animal breeding; autoantigens; autoimmune disorder; diabetes mellitus genetics; disease /disorder model; genetically modified animals; insulin dependent diabetes mellitus; leukocyte activation /transformation; model design /development; pancreatic islets; pathologic process; receptor expression; representational difference analysis; subtraction hybridization

DESCRIPTION (provided by applicant): The goal of the proposed project is to investigate mechanisms of pathogenesis and immunoregulation in autoimmune type 1 diabetes through the use of a T cell receptor transgenic (TCR-Tg) mouse expressing the alpha and beta chain genes from the T cell receptor of an islet specific, diabetogenic T cell clone, BDC-6.9. The T cell clone, BDC-6.9, is similar to another clone in our panel, BDC-2.5, in that it was derived from spleen cells of an NOD mouse, reacts with an antigen in the beta granule membrane, and rapidly induces disease when administered to young NOD mice or to NOD-scid recipients. The BDC-6.9 clone, unlike BDC-2.5, responds to islet antigen only from NOD or NOD-related mice and we have identified a microsatellite marker which is closely linked to the BDC-6.9 antigen on chromosome six. We have taken advantage of these findings to produce an NOD congenic (NOD.C6) mouse that lacks the BDC-6.9 autoantigen. Our aims under this project are to (1) characterize the properties of the 6.9 TCR-Tg mouse on the NOD background with respect to T cell function and disease incidence, (2) breed and characterize the 6.9 TCR-Tg mouse on the NOD.C6 congenic mouse lacking the target antigen, and (3) define the antigen for the BDC-6.9 antigen through analysis of differential gene expression in islets from NOD and NOD.C6 mice.

描述（由申请人提供）：拟议项目的目标是 探讨自身免疫型发病机制和免疫调节 通过使用T细胞受体转基因（TCR-Tg）小鼠， 从胰岛的T细胞受体表达α和β链基因 特异性致糖尿病T细胞克隆，BDC-6.9。T细胞克隆，BDC-6.9， 与我们小组中的另一个克隆BDC-2.5相似，因为它来自于 NOD小鼠的脾细胞与β颗粒中的抗原反应 膜，并迅速诱导疾病时，给予年轻的NOD小鼠或 NOD-scid受体。与BDC-2.5不同的是，BDC-6.9克隆对胰岛B细胞有反应。 抗原只从NOD或NOD相关小鼠，我们已经确定了一个 与BDC-6.9抗原紧密连锁的微卫星标记， 六号染色体我们利用这些发现来制作NOD C6小鼠，其缺乏BDC-6.9自身抗原。我们的目标在此 项目是（1）表征6.9 TCR-Tg小鼠在 NOD背景与T细胞功能和疾病发生率有关，（2）品种 并在缺乏TCR-Tg的NOD.C6同类小鼠上表征6.9 TCR-Tg小鼠。 靶抗原，和（3）通过以下步骤定义BDC-6.9抗原的抗原 来自NOD和NOD.C6小鼠的胰岛中差异基因表达的分析。