TYPE1 DIABETOGENIC GENES CENTROMERIC TO LMP2 IN NOD MICE

描述：（改编自研究者摘要）：1型糖尿病是一种 人类和NOD小鼠的多基因自身免疫性疾病。MHC中的基因 区域是最重要的，在确定敏感性或耐药性， 1型糖尿病NOD MHC I类的置换（同源重组） K区与R209 MHC I类K区的结合阻止了 糖尿病和胰岛炎。类似地 防止NOD A、E和D区域被R209区域取代 糖尿病和胰岛炎的发展。调查人员已经确定 6个同源NOD系，在R209/R209区域中具有纯合片段， 在Lmp 2-热点着丝粒的6.6 cM内，两个同源系具有一个 r209/r209的纯合片段在距离该区域3.3cM内， 着丝粒。他们的观察表明，除了MHC Ⅱ A类， 还有三个MHC连锁的1型糖尿病基因，两个在区域 在Lmp 2-热点的1.1 cM着丝粒内，一个在Lmp 2-热点的1.1 cM着丝粒内， 3.3 cM，从MHC外的着丝粒。前两种糖尿病之一 基因可以是MHC I类K基因本身，否则它们可以是两个非MHC I类K基因。 该地区的基因。他们提出的研究旨在进一步限制这些地区 包括MHC连锁的致糖尿病基因： 1.以确定MHC I K类分子本身是否是糖尿病的诱因。 (1)表达MHC I类分子的N3转基因NOD小鼠的建立和筛选 Kr 209（wm 7）对糖尿病的发展。 (2)胰岛炎的组织学检查及MHC I类分子的表达 N3转基因NOD小鼠中的Kr 209（wm 7）分子 (3)转基因Kr 209与固有r209/r209染色体的相互作用 在糖尿病和胰岛炎的发展中的同源线G中的片段 2.为了进一步缩小1.0 cM着丝粒区域至K（Iddla）， 在1.1 cM的着丝粒K（Idd 1b）和33 cM的区域内，从 MHC区域外的着丝粒（Iddlc）至<1.0 cM。 (1)通过将同源系C与NOD小鼠交配来产生新的重组小鼠， Iddla和Iddlb (2)通过将同源系G与NOD小鼠交配来产生新的重组小鼠， Iddlc

DESCRIPTION: (Adapted from the Investigator's abstract): Type 1 diabetes is a polygenic autoimmune disease in man and the NOD mouse. The genes in the MHC region are the most important in determining susceptibility or resistance to type 1 diabetes. Replacement (homologous recombination) of the NOD MHC class I K region with the R209 MHC class I K region prevented the development of diabetes and insulitis in the intra-MHC recombinant NOD mice. Similarly the replacement of the region of the NOD A, E and D with that of the R209 prevented the development of diabetes and insulitis. The investigators have established six congenic NOD lines with a homozygous segment of r209/r209 in the region of within 6.6 cM centromeric to the Lmp2-hotspot, and two congenic lines with a homozygous segment of r209/r209 in the region of within 3.3 cM from the centromere. Their observation suggests that in addition to the MHC class II A there are three more MHC-linked type 1 diabetogenic genes, two in the region of within 1.1 cM centromeric to the Lmp2 -hotspot, and one in the region of within 3.3 cM from the centromere outside the MHC. One of the first two diabetogenic genes may be the MHC class I K gene itself, otherwise they may be two non-MHC genes in the region. Their proposed studies aim to further restrict the regions including the MHC-linked diabetogenic genes: 1. To see whether the MHC class I K itself is diabetogenic. (1) Establish and screen N3 transgenic NOD mice expressing the MHC class I Kr209(wm7) for the development of diabetes. (2) Histological examination of insulitis and expression of the MHC class I Kr209(wm7) molecules in the N3 transgenic NOD mice (3) Interaction of the transgene Kr209 with the intrinsic r209/r209 chromosomal segment in the congenic line G in the development of diabetes and insulitis 2. To further narrow the region of within 1.0 cM centromeric to K (Iddla), within 1.1 cM centromeric to K(Idd1b) and the region of within 33 cM from the centromere outside the MHC region (Iddlc) to <1.0 cM. (1) Create new recombinant mice by mating the congenic line C with NOD mice for Iddla and Iddlb (2) Create new recombinant mice by mating the congenic line G with NOD mice for Iddlc