Congenic mapping identifies a novel Idd9 subregion regulating type 1 diabetes in NOD mice

被引：2
作者：
Lin, Bixuan [1 ]
Ciecko, Ashley E. [1 ]
MacKinney, Erin [1 ,2 ]
Serreze, David V. [3 ]
Chen, Yi-Guang [1 ]
机构：
[1] Med Coll Wisconsin, Dept Pediat, Max McGee Natl Res Ctr Juvenile Diabet, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
[2] Southern Illinois Univ, Sch Med, Springfield, IL 62702 USA
[3] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA
来源：
IMMUNOGENETICS | 2017年 / 69卷 / 03期
基金：
美国国家卫生研究院;
关键词：
Type; 1; diabetes; Idd9; Regulatory Tcells; NOD mouse; CD4(+)CD25(+) T-CELLS; DENDRITIC CELLS; SUSCEPTIBILITY; CONTRIBUTES; GENES; CD4; AUTOIMMUNITY; ASSOCIATION; CHILDREN; VARIANTS;
D O I：
10.1007/s00251-016-0957-3
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Type 1 diabetes (T1D) results from complex interactions between genetic and environmental factors. The nonobese diabetic (NOD) mouse develops spontaneous T1D and has been used extensively to study the genetic control of this disease. T1D is suppressed in NOD mice congenic for the C57BL/10 (B10)-derived Idd9 resistance region on chromosome 4. Previous studies conducted by other investigators have identified four subregions (Idd9.1, Idd9.2, Idd9.3, and Idd9.4) where B10-derived genes suppress T1D development in NOD mice. We independently generated and characterized six congenic strains containing B10-derived intervals that partially overlap with the Idd9.1 and Idd9.4 regions. T1D incidence studies have revealed a new B10-derived resistance region proximal to Idd9.1. Our results also indicated that a B10-derived gene(s) within the Idd9.4 region suppressed the diabetogenic activity of CD4 T cells and promoted CD103 expression on regulatory T cells indicative of an activated phenotype. In addition, we suggest the presence of a B10-derived susceptibility gene(s) in the Idd9.1/Idd9.4 region. These results provide additional information to improve our understanding of the complex genetic control by the Idd9 region.
引用
收藏
页码：193 / 198
页数：6
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