GENETICS AND PATHOLOGY OF NON-OBESE DIABETIC (NOD) MICE

描述（改编自研究者摘要）：虽然染色体 已经在小鼠中建立了许多非MHC基因的位置， 它们的实际身份和确切功能仍然未知。 电阻 3号染色体上的两个基因座IDD 3和IDD 10的等位基因共同赋予 在NOD中有很强的糖尿病保护作用。 同类小鼠有缺陷 在骨髓源性抗原的发育和成熟中 呈现 细胞（APC），包括巨噬细胞，足够严重 以削弱IL-1分泌反应。 这些缺陷在 IDD 3-IDD 10同类种群，导致假设， 这些等位基因的产物，在NOD H2的存在下， 有助于降低APC激活免疫调节的能力 途径。 该项目有三个目标。 首先是确定 NOD小鼠中哪些特定的巨噬细胞发育异常是 单独或协同防治IDD 3或IDD 10，使用 现有同类种群。 第二个目标将使用差异显示 分析以检测差异表达的基因。 第三 aim将使用骨髓嵌合体和胎儿胸腺器官培养， 研究受损APC的功能。

DESCRIPTION (Adapted from Investigator's abstract): Although chromosomal locations for a number of non-MHC genes have been established in mice, their actual identities and precise functions remain unknown. Resistance alleles at two loci on chromosome 3, IDD3 and IDD10, together confer strong diabetes protection in NOD. Congenic mice have defects in the development and maturation of marrow-derived antigen presenting cells (APC), including macrophages, sufficiently severe to impair IL-1 secretory responses. These defects are reversed in the IDD3-IDD10 congenic stock, leading to the hypothesis that products of these alleles, in the presence of the NOD H2, collectively contribute to reduced ability of APC to activate immunoregulatory pathways. This project has three aims. The first is to determine which specific macrophage developmental anomalies in NOD mice are individually or synergistically controlled by IDD3 or IDD10, using existing congenic stocks. The second aim will use differential display analysis to detect genes that are differentially expressed. The third aim will use bone marrow chimeras and fetal thymic organ culture to study the function of the impaired APC.