MHC-linked type 1 diabetes genes in NOD mice

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区域的基因在决定1型糖尿病的易感性或抵抗力方面是最重要的。将NOD MHC类IK区(同源重组)替换为R209 MHC类IK区，可预防MHC内重组NOD小鼠发生糖尿病和胰腺炎。类似地，用R209的NODA、E和D区域替换可以预防糖尿病和胰岛素炎的发生。我们在距LMP2热点7.4Mbp以内的区域建立了6个r209/r209纯合片段的同源系，在距着丝粒23Mbp以内的区域建立了两个r209/r209纯合片段的同源系。我们的观察表明，在LMP2基因着丝粒的33.9Mbp区域，除了MHC II A外，还有4个MHC连锁的1型糖尿病基因，分别是Idd1a、Idd1b、Idd1c和Idd1d。我们的研究旨在识别这四个基因，并研究它们在1型糖尿病发生发展中的作用。

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 of (homologous recombination) of the NOD MHC class IK region with the R209 MHC class IK 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. We have established six congenic lines with a homozygous segment of r209/r209 in the region of within 7.4 Mbp centromeric to the Lmp2-hotspot, and two congeniclines with homozygous segment of r209/r209 in the region of within 23 Mbp from the centromere. Our observation suggests that in addition to the MHC class II A there are four more MHC-linked type 1 diabetogenic genes in the 33.9 Mbp region centromeric to the Lmp2 gene, Idd1a, Idd1b, Idd1c and Idd1d. Our study aims to identify the four genes and examine their functions in the development of type 1 diabetes.