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

• Project/Area Number: 20390112
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Ehime University
• Principal Investigator: NOSE Masato Ehime University, プロテオ医学研究センター, 教授 (70030913)
• 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)
• Co-Investigator(Renkei-kenkyūsha): ONO Masao 東北大学, 大学院・医学系研究科, 教授 (20302218)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥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)
• 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

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.

Research Products

• [Journal Article] Evaluating the role of rheumatoid factors in the development of rheumatoidarthritis in a mouse model with a newly established ELISA system. (2010)
  • Author(s): Tanaka Y, Komori H, Mori S, Soga Y, Tsubaki T, Terada M, Miyazaki T, Fujino T, Nakamura S, Kanno H, Sawasaki T, Endo Y, Nose M.
  • Journal Title: Tohoku J Exp Med. 220 Pages: 199-206
  • Peer Reviewed
• [Journal Article] Simple screening method for autoantigen proteins using the N-terminal biotinylated protein library produced by wheat Cell-Free synthesis. (2010)
  • Author(s): Matsuoka K, Komori H, Nose M, Endo Y, Sawasaki T.
  • Journal Title: J Proteome Res. 9 Pages: 4264-4273
  • Peer Reviewed
• [Journal Article] Evaluating the role of rheumatoid factors in the development of rheumatoidarthritis in a mouse model with a newly established ELISA system. (2010)
  • Author(s): Tanaka Y, Komori H, Mori S, Soga Y, Tsubaki T, Terada M, Miyazaki T, Fujino T, Nakamura S, Kanno H, Sawasaki T, Endo Y, Nose M.
  • Journal Title: Tohoku J Exp Med. Volume: 220 Pages: 199-206
  • Peer Reviewed
• [Journal Article] Simple screening method for autoantigen proteins using the N-terminal biotinylated protein library produced by wheat Cell-Free synthesis. (2010)
  • Author(s): Matsuoka K, Komori H, Nose M, Endo Y, Sawasaki T.
  • Journal Title: J Proteome Res. Volume: 9 Pages: 4264-4273
  • Peer Reviewed
• [Journal Article] Evaluating the role of rheumatoid factors in the development of rheumatoidarthritis in a mouse model with a newly established ELISA system (2010)
  • Author(s): Tanaka Y, Komori H, Mori S, Soga Y, Tsubaki T, Terada M, Miyazaki T, Fujino T, Nakamura S, Kanno H, Sawasaki T, Endo Y, Nose M.
  • Journal Title: Tohoku J Exp Med 220 Pages: 199-206
  • Peer Reviewed
• [Journal Article] Role of SLAM-associated protein in the pathogenesis of autoimmune diseases and immunological disorders (2010)
  • Author(s): Furukawa H, Tohma, S Kitazawa H, Komori H, Nose M, Ono M.
  • Journal Title: Arch Immunol Ther Exp 58 Pages: 37-44
  • Peer Reviewed
• [Journal Article] Toll-Like receptor 3 signaling induces chronic pancreatitis through the Fas/Fas ligand-mediated cytotoxicity. (2009)
  • Author(s): Soga Y, Komori H, Miyazaki T, Arita N, Terada M, Kamada K, Tanaka Y, Fujino T, Hiasa Y, Matsuura B, Onji M, Nose M.
  • Journal Title: Tohoku J Exp Med. 217(3) Pages: 175-184
  • NAID: 10025105148
  • Peer Reviewed
• [Journal Article] Genetic dissociation of dacryoadenitis and sialadenitis in a sjogren's syndrome mouse model with common and different susceptibility gene loci. (2009)
  • Author(s): Kamao T, Miyazaki T, Soga Y, Komori H, Terada M, Ohashi Y, Nose M.
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 3257-3265
  • Peer Reviewed
• [Journal Article] Toll-Like receptor 3 signaling induces chronic pancreatitis through the Fas/Fas ligand-mediated cytoxicity (2009)
  • Author(s): Soga Y, Komori H, Miyazaki T, Arita N, Terada M, Kamada K, Tanaka Y, Fujino T, Hiasa Y, Matsuura B, Onji M, Nose M.
  • Journal Title: Tohoku J.Exp. Med. 217 Pages: 175-184
  • Peer Reviewed
• [Journal Article] Genetic dissociation of dacryoadenitis and sialadenitis in a sjogren's syndrome mouse model with common and different susceptibility gene loci (2009)
  • Author(s): Kamao T, Miyazaki T, Soga Y, Komori H, Terada M, Ohashi Y, Nose M.
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 3257-3265
  • Peer Reviewed
• [Journal Article] モデルマウスから学ぶ血管炎のゲノム的仕組み (2009)
  • Author(s): 能勢眞人, 小森浩章
  • Journal Title: J Jpm Coll Angiol 49 Pages: 11-16
  • NAID: 10025626686
• [Journal Article] 血管炎発症のポリジーンネットワークモデル (2009)
  • Author(s): 能勢眞人, 小森浩章
  • Journal Title: リウマチ科 42 Pages: 337-343
• [Journal Article] Toll-Like receptor 3 signaling induces chronic pancreatitis through the Fas/Fas ligand-mediated cytotoxicity. (2009)
  • Author(s): Soga Y, Komori H, Nose M, et al
  • Journal Title: Tohoku J. Exp. Med 217 Pages: 175-184
  • NAID: 10025105148
  • Peer Reviewed
• [Journal Article] Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model. (2008)
  • Author(s): Hasegawa H, Inoue A, Kohno M, Lei J, Miyazaki T, Yoshie O, Nose M, Yasukawa M.
  • Journal Title: Gene Ther. 15 Pages: 171-182
  • Peer Reviewed
• [Journal Article] Dcir deficiency causes development of autoimmune diseases in mice due to excess expanision of dendritic cells. (2008)
  • Author(s): Fujikado N, Saijo S, Yonezawa T, Shimamori K, Ishii A, Sugai S, Kotaki H, Sudo K, Nose M, Iwakura Y.
  • Journal Title: Nature medicine. 14 Pages: 176-180
  • Peer Reviewed
• [Journal Article] Novel recombinant congenic mouse strain developing arthritis with enthesopathy. (2008)
  • Author(s): Mori S, Tanda N, Ito R.M, Oishi H, Tsubaki T, Komori H, Zhang MC, Ono M, Nishimura M, Nose M.
  • Journal Title: Pathology Int. 58 Pages: 407-414
  • NAID: 10027377068
  • Peer Reviewed
• [Journal Article] Evaluation of the ameliorative effects of immunosuppressants on crescentic giomerulonephritis in SCG/Kj mice. (2008)
  • Author(s): Saiga K, Yoshida M, Nakamura I, Toyoda E, Tokunaka K, Morihashi H, Abe F, Nemoto K, Nose M.
  • Journal Title: Int Immunopharmacol. 8 Pages: 1183-1189
  • Peer Reviewed
• [Journal Article] Mast cell hyperplasia in the skin of Dsg4-deficient hypotrichosis mice, which are long-living mutants of lupus-prone mice. (2008)
  • Author(s): Zhang MC, Furukawa H, Tokunaka K, Saiga K, Date F, Owada Y, Nose M, Ono M.
  • Journal Title: Immunogenetics. 60 Pages: 599-607
  • Peer Reviewed
• [Journal Article] Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model. (2008)
  • Author(s): Hasegawa H, Inoue A, Nose M, et al
  • Journal Title: Gene Ther. 15 Pages: 171-182
  • Peer Reviewed
• [Journal Article] Dcir deficiency causes development of autoimmune diseases in mice due to excess expanision of dendritic cells. (2008)
  • Author(s): Fujikado N, Saijo S, Nose M, et al
  • Journal Title: Nature medicine. 14 Pages: 176-180
  • Peer Reviewed
• [Journal Article] Novel recombinant congenic mouse strain developing arthritis with enthesopathy. (2008)
  • Author(s): Mori S, Tanda N, Nose M, et al
  • Journal Title: Pathology Int. 58 Pages: 407-414
  • NAID: 10027377068
  • Peer Reviewed
• [Journal Article] Evaluation of the ameliorative effects of immunosuppressants on crescentic giomerulonephritis in SCG/Kjmice. (2008)
  • Author(s): Saiga K, Yoshida M, Nose M, et al
  • Journal Title: International Immunopharmacology. 8 Pages: 1183-1189
  • Peer Reviewed
• [Journal Article] Mast cell hyperplasia in the skin of Dsg4-deficient hypotrichosis mice, which are long-living mutants, of lupus-prone mice. (2008)
  • Author(s): Zhang M-C, Furukawa H, Nose M, et al
  • Journal Title: Immunogenetics. 60 Pages: 599-607
  • Peer Reviewed
• [Presentation] Common and different gene loci susceptible to sialoadenitis and dacryoadenitis in a sjogen's syndrome mouse model. (2010)
  • Author(s): Kamao T, Miyazaki T, Soga Y, Komori H, Terada M, Nose M
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan.
• [Presentation] A novel mouse model for primary focal segmental glomerulosclerosis developing associated with insertional mutagenesis by transgene. (2010)
  • Author(s): Tanaka Y, Fujino T, Terada M, Ito M, Shudo M, Okabe M, Nose M
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan.
• [Presentation] Allelic polymorphism of murine osteopontin implicates functional differences in antigen presentation by dendritic cells. (2010)
  • Author(s): Miyazaki T, Tanaka Y, Kurata M, Ono M, Nose M
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan.
• [Presentation] オステオポンチン蛋白多型による樹状細胞抗原提示能修飾の新たなメカニズム (2009)
  • Author(s): 宮崎龍彦、田中ゆき、小野栄夫、能勢眞人
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
• [Presentation] 血管炎に関する基礎研究の進歩 (2009)
  • Author(s): 能勢眞人
  • Organizer: 第50回日本脈管学会総会
  • Place of Presentation: 東京
• [Presentation] 膠原病のポリジーンネットワーク (2009)
  • Author(s): 能勢眞人
  • Organizer: 第37回日本臨床免疫学会総会
  • Place of Presentation: 東京
• [Presentation] A simple capture ELISA for recombinant proteins synthesized in cell-free system : Genetic dissociation of rheumatoid factors from arthritis in MRL/lpr mice. (2009)
  • Author(s): 田中ゆき, 曽我美子, 能勢眞人
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] オステオポンチン蛋白多型による樹状細胞抗原提示能修飾の新たなメカニズム (2009)
  • Author(s): 宮崎龍彦, 田中ゆき, 小野栄夫, 能勢眞人
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都(国立京都国際会館)
• [Presentation] 血管炎に関する基礎研究の進歩(シンポジウム) (2009)
  • Author(s): 能勢眞人
  • Organizer: 第50回日本脈管学会総会
  • Place of Presentation: 東京(ハイアットリージェンシー東京)
• [Presentation] 膠原病のポリジーンネットワーク(シンポジウム) (2009)
  • Author(s): 能勢眞人
  • Organizer: 第37回日本臨床免疫学会総会
  • Place of Presentation: 東京(東京ステーションコンファレンス)
• [Presentation] Common and different gene loci susceptible to sialoadenitis and dacryoadenitis in a sjogren's syndrome mouse model. (2008)
  • Author(s): Kamao T, Miyazaki T, Soga Y, Komori H, Terada M, Nose M
  • Organizer: 6th International Congress on Autoimmunity
  • Place of Presentation: Porto, Portugal.
• [Presentation] Genetic basis of autoimmune pancreatitis induced by the stimulation through the toll-like receptor 3 signaling. (2008)
  • Author(s): Soga Y, Komori H, Terada T, Miyazaki T, Nose M
  • Organizer: 6th International Congress on Autoimmunity
  • Place of Presentation: Porto, Portugal.
• [Presentation] 自然免疫系刺激により誘導される自己免疫性膵炎の疾患感受性遺伝子解析 (2008)
  • Author(s): 小森浩章、曽我美子、能勢眞人
  • Organizer: 第97回日本病理学会総会(日本病理学会会誌第97巻第1号p169.)
  • Place of Presentation: 金沢
• [Presentation] 血管炎発症のポリジーンネットワークモデル (2008)
  • Author(s): 能勢眞人
  • Organizer: 第52回日本リウマチ学会総会・学術集会・第17回国際リウマチシンポジウム
  • Place of Presentation: 札幌
• [Presentation] Genetic basis of autoimmnune pancreatitis induced by the stimulation through the toll-like receptor 3 signaling. (2008)
  • Author(s): Soga Y, Komori H, Nose M, et al
  • Organizer: 6^<th> Intemational Congress on Autoimmunity
  • Place of Presentation: Porto, Portugal.
• [Presentation] Common and different gene loci susceptible to sialoadenitis and dacryoadenitis in a sjogern's syndrome mouse model. (2008)
  • Author(s): Kamao T, Miyazaki T, Nose M, et al
  • Organizer: 6^<th> International Congress on Autoimmunity
  • Place of Presentation: Porto, Portugal.
• [Book] リウマチ病学テキスト (2010)
  • Author(s): 能勢眞人
  • Total Pages: 8
  • Publisher: 診断と治癒社