Resistance genes to collagen disease in a wild mice-derived inbred strain MSM/Ms

野生小鼠近交系 MSM/Ms 中胶原蛋白病的抗性基因

• 批准号: 20390112
• 负责人: NOSE Masato
• 金额: $ 12.31万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390112/
• 关键词: MRL; lpr; MSM; Ms; 糸球体腎炎; QTL解析; 位置的候補遺伝子; Cd59a; プロモーター多型; リコンビナントコンジェニックマウス; MRL/lpr; MSM/Ms; 血管炎; リコンビナント温ジェニックマウス; 系球体腎炎; 抗Cd59a抗体; 1pr; CD59; ルチフェラーゼアッセイ

This study attempted to elucidate the polygenic genetic resistance of a wild mice-derived inbred strain MSM/Ms, having a larger gene pools than commonly used laboratory mouse strains, to glomerulonephritis in an MRL/Mp-lpr/lpr (MRL-Fas^<lpr>) lupus strain of mice and thereby to understand the steps controlling development of lupus nephritis. A genome wide scan for glomerulonephritis resistance loci in a dominant inheritance form was carried out by using MRL-Fas^<lpr> x (MRL-Fas^<lpr> x MSM/Ms) F1 backcross mice. Three dominant MSM/Ms resistance loci were mapped on chromosomes 2, 13 and 4. One of the candidate genes for the locus Agnmrl was Cd59a, encoding an glycosyl phosphatidylinositol-anchored glycoprotein inhibiting the membrane attack complex of complement. Expression of Cd59a in the glomeruli was higher in MSM/Ms than in MRL-Fas^<lpr>. Different transcriptional activity of the Cd59a promoter region was observed between the parental strains of mice. Then, the recombinant congenic strain of mice MRL-Fas^<lpr>-Cd59a^<MSM> was newly established, which was significantly decreased in severity of glomerulonephritis and also renal vasculitis.

本研究试图阐明野生小鼠来源的近交系MSM/Ms（具有比常用实验室小鼠品系更大的基因库）对MRL/Mp-lpr/lpr（MRL-Fas ^）狼疮小鼠品系中的肾小球肾炎的多基因遗传抗性<lpr>，从而理解控制狼疮肾炎发展的步骤。利用MRL-Fas^ x（MRL-Fas ^ x MSM/Ms）F1回交小鼠进行显性遗传形式的肾小球肾炎抗性基因座的全基因组扫描<lpr><lpr>。3个显性抗MSM/Ms基因位点分别位于第2、13和4染色体上。位点Agnmrl的候选基因之一是Cd 59 a，其编码抑制补体的膜攻击复合物的糖基磷脂酰肌醇锚定糖蛋白。MSM/Ms肾小球中Cd 59 a的表达高于MRL-Fas<lpr>。不同的转录活性的Cd 59 a启动子区域之间的亲本品系的小鼠观察。然后，新建立了重组小鼠MRL-Fas^<lpr>-Cd 59 a ^<MSM>同类系，其肾小球肾炎和肾血管炎的严重程度显着降低。

项目成果

血管炎に関する基礎研究の進歩

血管炎基础研究进展

• 发表时间: 2009
• 作者: Tsunekawa S;Ohi Y;Ishii Y;Sasahara M;Haji A.;能勢眞人
• 通讯作者: 能勢眞人

Mast cell hyperplasia in the skin of Dsg4-deficient hypotrichosis mice, which are long-living mutants of lupus-prone mice

• DOI: 10.1007/s00251-008-0320-4
• 发表时间: 2008-08
• 期刊: Immunogenetics
• 影响因子: 3.2
• 作者: Ming-Cai Zhang;H. Furukawa;K. Tokunaka;K. Saiga;F. Date;Y. Owada;M. Nose;M. Ono

Genetic basis of autoimmune pancreatitis induced by the stimulation through the toll-like receptor 3 signaling.

通过 Toll 样受体 3 信号传导刺激诱发的自身免疫性胰腺炎的遗传基础。

• 发表时间: 2008
• 作者: Soga Y;Komori H;Terada T;Miyazaki T;Nose M
• 通讯作者: Nose M

Dcir deficiency causes development of autoimmune diseases in mice due to excess expanision of dendritic cells

DCIR 缺陷导致小鼠因树突状细胞过度扩张而患上自身免疫性疾病

• 发表时间: 2008
• 期刊: Nature Medicine 14(2)
• 作者: Fujikado N;Saijo S;Nose M;et. al.
• 通讯作者: et. al.

Genetic basis of autoimmnune pancreatitis induced by the stimulation through the toll-like receptor 3 signaling.

通过 Toll 样受体 3 信号传导刺激诱发的自身免疫性胰腺炎的遗传基础。

• 发表时间: 2008
• 作者: Soga Y;Komori H;Nose M;et al
• 通讯作者: et al