MHC-linked type 1 diabetes genes in NOD mice

NOD 小鼠中 MHC 相关 1 型糖尿病基因

• 批准号: 22500399
• 负责人: HATTORI Masakazu
• 金额: $ 2.75万
• 依托单位: Department of Clinical Research, National Hospital Organization Kyoto Medical Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22500399/
• 关键词: 糖尿病; 動物; 遺伝学; 免疫学; 内科; 1型糖尿病; NODマウス; 糖尿病感受性遺伝子; MHC連鎖遺伝子; B10.A(R209)マウス; Lmp2連鎖組換ホットスポット; Idd1a, b, c,d; 遺伝子発現

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.

1型糖尿病是人类和NOD小鼠的多基因自身免疫性疾病。MHC区域中的基因在决定1型糖尿病的易感性或抵抗性方面是最重要的。用R209 MHC IK类区域替换（同源重组）NOD MHC IK类区域防止了MHC内重组NOD小鼠中糖尿病和胰岛炎的发展。类似地，用R209的区域替换NOD A、E和D的区域防止了糖尿病和胰岛炎的发展。我们已经建立了6个在Lmp 2-hotspot着丝粒7.4Mbp范围内具有r209/r209纯合片段的同源系和2个在Lmp 2-hotspot着丝粒23 Mbp范围内具有r209/r209纯合片段的同源系。我们的观察表明，除了MHC II A类，还有四个MHC连锁的1型糖尿病基因在33.9 Mbp区域着丝粒Lmp 2基因，Idd 1a，Idd 1b，Idd 1c和Idd 1d。我们的研究旨在确定这四个基因，并检查它们在1型糖尿病发展中的功能。

项目成果

The 6th USA-Japan Meeting on Diabetes at Kyoto Medical Center, March 17-18, 2012

第六届美日糖尿病会议于 2012 年 3 月 17-18 日在京都医学中心举行

Metallo-allixinate complexes with anti-diabetic and anti-metabolic syndrome activities.

具有抗糖尿病和抗代谢综合征活性的金属蒜氨酸复合物。

• 发表时间: 2010
• 期刊: Metallomics (The Royal Society of Chemistry)
• 作者: Sakurai H;Katoh A;Kiss T;Jakusch T;Hattori M.
• 通讯作者: Hattori M.

生活習慣病に対する新しい治療 DPP-IV阻害薬:2型糖尿病治療におけるインクレチン分解抑制の重要性

生活方式相关疾病新疗法DPP-IV抑制剂：抑制肠促胰素降解在治疗2型糖尿病中的重要性

• 发表时间: 2010
• 期刊: Journal of Integrated Medicine (JIM)
• 作者: 服部正和;知念良直;中川嘉苗;島津章;桜井弘;William Sullivan
• 通讯作者: William Sullivan

生活習慣に対する新しい治療、DPP-IV阻害薬 : 2型糖尿病治療におけるインクレチン分解抑制の重要性

DPP-IV抑制剂，治疗生活习惯的新疗法：抑制肠促胰素降解在治疗2型糖尿病中的重要性

• 发表时间: 2010
• 期刊: Journal of Integrated Medicine (JIM).
• 作者: 服部正和;知念良直;中川嘉苗;島津章;桜井弘;William Sullivan.
• 通讯作者: William Sullivan.

Predominant occupation of the class I MHC molecule H-2Kwm7 with a single self-peptide suggests a mechanism for its diabetes-protective effect

• DOI: 10.1093/intimm/dxp127
• 发表时间: 2010-03-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Brims, Daniel R.;Qian, Jie;DiLorenzo, Teresa P.
• 通讯作者: DiLorenzo, Teresa P.