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

点击翻译按钮获取中文摘要

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.