DISSECTION OF IDD PATHOGENESIS WITH CONGENIC STRAINS

同源菌株 IDD 发病机制的剖析

• 批准号: 2151060
• 负责人: Edward K. Wakeland
• 金额: $ 16.57万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2151060
• 关键词: animal breeding; autoantibody; bone marrow transplantation; diabetes mellitus genetics; disease /disorder model; genetic mapping; genetic recombination; genetic strain; insulin dependent diabetes mellitus; laboratory mouse; prediabetic state

DESCRIPTION (Adapted from Investigator's abstract): Six NOD-derived genomic intervals have been identified and introduced into C57Bl/6 congenic strains. Each of these intervals contains a locus contributing to diabetes susceptibility in the NOD, and the congenic strains will be inter-crossed to produce a collection of polycongenic strains containing various combinations of these NOD-derived intervals. Each strain will be assessed for insulitis, IDD susceptibility, and the expression of a variety of IDD-associated autoimmune phenotypes including the production of autoantibodies specific for GAD and insulin. Pathologic properties of each polycongenic strain that develops either spontaneous or cyclophosphamide-induced IDD will be studied to test the hypothesis that susceptibility is inherited as a threshold liability in which multiple distinct combinations of susceptibility alleles can result in IDD and insulitis. Additional aims will study the role of these same intervals in modulating autoimmunity by bone marrow reconstitution of NOD mice with T depleted bone marrow from the polycongenic strains, and a final aim will produce additional congenic recombinants for each genomic interval to improve the map position of susceptibility loci.

描述（改编自研究者的摘要）：六种 NOD 衍生的 基因组区间已被确定并引入 C57Bl/6 同源菌株。每个区间都包含一个轨迹 导致 NOD 中的糖尿病易感性，以及同类 菌株将相互杂交以产生多同源的集合 含有这些 NOD 衍生区间的各种组合的菌株。 将评估每种菌株的胰岛素炎、IDD 易感性和 多种 IDD 相关自身免疫的表达 表型，包括 GAD 特异性自身抗体的产生 和胰岛素。 每个多同源菌株的病理特性 发生自发性或环磷酰胺诱发的 IDD 研究目的是检验易感性是遗传性的假设 阈值责任，其中多种不同的组合 易感等位基因可导致 IDD 和胰岛素炎。 额外的 目标将研究这些相同的间隔在调节中的作用 T 耗尽的 NOD 小鼠骨髓重建的自身免疫 来自多同源菌株的骨髓，最终目标是 为每个基因组间隔产生额外的同源重组体 改善易感位点的图谱位置。