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: 6621072
• 负责人: KATHRYN M HASKINS
• 金额: $ 20.6万
• 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 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621072
• 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 研究自身免疫型的发病机制和免疫调节机制 1 通过使用 T 细胞受体转基因 (TCR-Tg) 小鼠治疗糖尿病 表达来自胰岛 T 细胞受体的 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 是 与我们面板中的另一个克隆 BDC-2.5 类似，因为它源自 NOD 小鼠的脾细胞与 β 颗粒中的抗原发生反应 膜，当给予年轻的 NOD 小鼠或 NOD-scid 接收者。与 BDC-2.5 不同，BDC-6.9 克隆对胰岛有反应 仅来自 NOD 或 NOD 相关小鼠的抗原，我们已经鉴定出 与 BDC-6.9 抗原紧密连锁的微卫星标记 第六号染色体。我们利用这些发现制定了 NOD 缺乏 BDC-6.9 自身抗原的同源 (NOD.C6) 小鼠。我们在此下的目标 项目的目的是 (1) 表征 6.9 TCR-Tg 小鼠的特性 关于 T 细胞功能和疾病发病率的 NOD 背景，(2) 品种 并在缺乏 6.9 TCR-Tg 小鼠的 NOD.C6 同类小鼠上表征 目标抗原，以及 (3) 通过以下方式定义 BDC-6.9 抗原： NOD 和 NOD.C6 小鼠胰岛中差异基因表达的分析。