| Project/Area Number |
20390112
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Ehime University |
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Principal Investigator |
NOSE Masato Ehime University, プロテオ医学研究センター, 教授 (70030913)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Tatsuhiko 愛媛大学, 大学院・医学系研究科, 准教授 (80239384)
SOGA Yoshiko 愛媛大学, 医学部附属病院, 助教 (10549182)
小森 浩章 愛媛大学, 大学院・医学系研究科, 講師 (30372725)
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| Co-Investigator(Renkei-kenkyūsha) |
ONO Masao 東北大学, 大学院・医学系研究科, 教授 (20302218)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2008: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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