TYPE1 DIABETOGENIC GENES CENTROMERIC TO LMP2 IN NOD MICE

描述：(改编自调查人员摘要)：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 在决定对甲氧西林的易感性或抗药性方面，区域是最重要的 1型糖尿病。NOD MHC I类基因的替换(同源重组) K区与R209 MHC I类K区共同阻碍了 MHC内注射重组NOD小鼠的糖尿病和胰腺炎。类似地， 防止将节点A、E和D的区域替换为R209的区域 糖尿病和胰岛炎症的发展。调查人员已经确定 6个含有r209/r209纯合子片段的同源节系 在LMP2热点的着丝粒6.6 cM范围内，以及两个具有 R209/r209纯合子片段位于距R209基因3.3 cM以内的区域 着丝粒。他们的观察表明，除了MHC II A类 另外还有三个MHC连锁的1型糖尿病基因，其中两个位于 在LMP2-热点的着丝粒1.1 cM以内，以及在LMP2-热点的区域内 距着丝粒3.3 cm的MHC。最早的两种糖尿病诱因之一 基因可能是MHC K类基因本身，否则可能是两个非MHC 该区域的基因。他们提出的研究旨在进一步限制这些地区 包括MHC连锁的糖尿病致病基因： 1.观察MHC-K类分子本身是否具有糖尿病的致病作用。 (1)建立并筛选表达MHC-I类基因的N3转基因NOD小鼠 Kr209(Wm7)用于糖尿病的发展。 (2)组织学检查及MHC-I类分子的表达 N3转基因NOD小鼠体内的Kr209(Wm7)分子 (3)转基因Kr209与固有r209/r209染色体的相互作用 G同源基因片段与糖尿病和胰岛素炎的关系 2.为了进一步缩小着丝粒为K(Iddla)的1.0 cm以内的区域， 在着丝粒到K(Idd1b)的1.1厘米范围内，以及距离 着丝粒在MHC区域外(Iddlc)到&lt；1.0厘米。 (1)将同源品系C与NOD小鼠杂交，产生新的重组小鼠 Iddla和Iddlb (2)将同源品系G与NOD小鼠杂交，产生新的重组小鼠 懒惰

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