Elucidation of susceptibility gene for type 1 diabetes mellitus by integration of functional analysis of recombinant chromosome with bioinformatics

主要组织相容性复合体（MHC）连锁染色体区域在人和NOD小鼠（1型糖尿病动物模型）中都具有强烈的1型糖尿病遗传易感性。通过研究一个基因NOD。CTS- h -2系的MHC染色体区域来源于与NOD小鼠具有相同MHC II类的CTS小鼠，我们已经证明MHC相关的强易感性是由多个基因赋予的，NOD在II类区域外有一个易感性基因，称为Idd16。在本项目中，我们明确了以下几点：通过选育，建立了2个亚同源系（NOD）。CTS-H2R1和NOD。CTS-H2R2)与新的重组染色体亚基因系NOD糖尿病的发展。2 .与nod型窝鼠（对照组）相比，CTS-H2R1被抑制相反，对于其他亚同源系NOD。CTS-H2R2，其糖尿病的发展情况以及胰岛素的程度与nod型（对照组）没有显著差异综合这些数据，Iddl6进一步定位到与II类区相邻但又不同的区域（1.62 + 0.24cM），即疾病易感区域建立新的亚同源NOD。CTS-H2系基因间隔较短，有利于进一步缩小Idd16的定位范围。

Major histocompatibility complex (MHC)-linked chromosomal region confers strong genetic predisposition to type 1 diabetes mellitus both in human and NOD mouse, an animal model for type 1 diabetes. By investigating a congenic NOD.CTS-H-2 line whose chromosomal region encompassing the MHC is derived from the CTS mouse with the identical MHC class II to the NOD mouse, we have shown that the MHC-linked strong susceptibility is conferred by multiple genes and NOD has a susceptibility gene(s) outside class II region, termed Idd16. In the present project, we have clarified the following points ;1 We established, by selective breeding, two subcongenic lines (NOD.CTS-H2R1 and NOD.CTS-H2R2) with new recombinant chromosomes.2 The development of diabetes of the sub congenic line NOD.CTS-H2R1 was suppressed compared to that of the NOD-type littermates (control).3 In contrast, as for the other subcongenic line NOD.CTS-H2R2, it's development of diabetes as well as the degree of insulitis were not significantly different from that of the NOD-type littermates (control).4 Taken these data together, Iddl6 was further mapped to the region (1.62 + 0.24cM) adjacent to but distinct from the class II region, to the disease susceptibility.5 Establishment of a new subcongenic NOD.CTS-H2 line with a shorter congenic interval facilitates further narrowing down of the localization of Idd16.