权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

重组染色体功能分析与生物信息学相结合阐明1型糖尿病易感基因

基本信息

批准号：
17590929
负责人：
FUJISAWA Tomomi
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

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.

主要组织相容性复合体（MHC）连锁的染色体区域赋予人和NOD小鼠（1型糖尿病的动物模型）1型糖尿病的强烈遗传易感性。通过研究同源NOD.CTS-H-2系，其包含MHC的染色体区域来自具有与NOD小鼠相同的MHC II类的CTS小鼠，我们已经表明MHC连锁的强易感性由多个基因赋予，并且NOD具有在II类区域之外的易感基因，称为Idd 16。在本项目中，我们明确了以下几点：1通过选择育种，建立了两个亚近缘系（NOD. CTS-H2 R1和NOD. CTS-H2 R2）。2亚同源系NOD. CTS-H2 R1的糖尿病发展与NOD型同窝仔（对照）相比受到抑制。3相反，对于其它亚同源系NOD. CTS-H2 R2，其糖尿病的发展以及胰岛炎的程度与NOD型同窝仔（对照）的糖尿病发展以及胰岛炎的程度没有显著差异。4综合这些数据，Idd 16被进一步定位于该区域（1.62 ± 0.24cM）与Ⅱ类区相邻但不同，5建立一个新的亚同源NOD.CTS-H2系，具有较短的同源间隔，有助于进一步缩小Idd 16的定位。