• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Research of rheumatoid arthritis using Dbl knock-out mice

Research Project

Project/Area Number 15591055
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKobe University

Principal Investigator

HASHIRAMOTO Akira  Kobe Univ., FHS School of Med., Visiting Associate Professor, 医学部, 客員助教授 (80346246)

Co-Investigator(Kenkyū-buntansha) MIURA Yasushi  Kobe Univ., FHS School of Med., Visiting Associate Professor, 医学部, 客員助教授 (60346244)
KOMAI Koichiro  Kobe Univ., FHS School of Med., Assistant, 医学部, 助手 (40304117)
村田 美紀  神戸大学, 医学部, 寄付講座教員 (70346245)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsDbl / Rheumatoid arthritis / 遺伝子除去マウス
Research Abstract

Rheumatoid arthritis (RA) is a chronic polyarthritis finally leading to joint destruction. While the ratio of the risk for siblings of patients with a disease was much greater in familial RA, suggesting that genetic factors may be important as a cause of familial clustering, we have previously reported in Japanese familial RA with 3 principal chromosomal regions of linkage, D1S253/214, D8S556 and DXS1232. Komai et al. have subsequently identified DBL proto-oncogene (wild type DBL; GenBank/EMBL/DDBJ Accession No.AB085902) located on DXS1232/984 as a candidate for RA disease gene : a mutant DBL cDNA lacking exons 23 and 24 (deleted type DBL ; GenBank/EMBL/DDBJ Accession No. AB085901) was associated with familial RA.
The DBL proto-oncogene is a prototype guanine nucleotide exchange factor (GEF) that modulates activity of small G proteins, including Rho family GTPases, RhoA and Cdc42 and possibly Rac1. Dbl converts the client proteins from the GDP-bound (inactive) form to the GTP-bound (act … More ive) form, allowing its effector domain to interact with downstream signaling molecules. Previous studies have shown that the Rho family GTPases control actin cytoskeleton organization and modulate movement, proliferation, and apoptosis of the cell. In humans, Rho family GEFs play important roles in the maturation and organization of skeletal muscles or nerves, also in the maturation and cytokine production of lymphoid cells. The mutation in some of the GEF family genes has been implicated in the human disease such as faciogenital dysplasia ^<15)>. It have been reported that deleted form of Dbl showed a weaker GEF activity toward Cdc42, and that infiltration and NADPH oxidase activity of neutrophils were significantly decreased in rheumatoid patients with this deleted mutant DBL.
In the present study, we established mouse embryonic fibroblast(MEF) cell lines from Dbl knock-out mice and evaluated the activity of Rho family proteins and the intracellular localization and mobility of Dbl protein in mutant or wild type MEFs. The result showed that Dbl proto-oncogene affect the activation of Rho family proteins in MEFs through the decrease of intracellular mobility. We are now going to back-cross Dbl knock-out mice with DBIJ mice to examine the effects of Dbl gene-deletion on collagen-induced arthritis in mice. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (15 results)

All 2005 2004 Other

All Journal Article (12 results) Publications (3 results)

  • [Journal Article] Heat shock protein 90 (HSP9O) is required for increased DNA binding activity of activator protein-1 (AP-1), a heterodimer of Fos/JunD, in rheumatoid synovial cells under inflammatory stimuli2005

    • Author(s)
      Murata M
    • Journal Title

      Int.J.Mol.Med. 15

      Pages: 649-653

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Estrogen specifically stimulates expression and production of Osteoprotegerin from rheumatoid synovial fibroblasts2005

    • Author(s)
      Mitani M
    • Journal Title

      Int.J.Mol.Med. 15

      Pages: 827-832

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heat shock protein 90 (HSP90) is required for increased DNA binding activity of activator protein-1 (AP-1), a heterodimer of Fos/JunD, in rheumatoid synovial cells under inflammatory stimuli.2005

    • Author(s)
      Miki, Murata
    • Journal Title

      Int.J.Mol.Med. 15

      Pages: 649-653

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Estrogen specifically stimulates expression and production of Osteoprotegerin from rheumatoid synovial fibroblasts.2005

    • Author(s)
      Makoto, Mitani
    • Journal Title

      Int.J.Mol.Med. 15

      Pages: 827-832

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Linkage解析によるRA関連遺伝子2005

    • Author(s)
      柱本照
    • Journal Title

      ゲノム医学 5.1

      Pages: 33-38

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3 : gene duplication is more prevalent in rheumatoid arthritis2004

    • Author(s)
      Osawa K
    • Journal Title

      Genes Immun 5.6

      Pages: 439-443

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A case of central nervous system lupus in succession to lupus nephritis2004

    • Author(s)
      Murata M
    • Journal Title

      Mod Rheumatol 14.4

      Pages: 323-326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3 : gene duplication is more prevalent in rheumatoid arthritis.2004

    • Author(s)
      Kayo, Osawa
    • Journal Title

      Genes Immun 5(6)

      Pages: 439-443

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A case of central nervous system lupus in succession to lupus nephritis.2004

    • Author(s)
      Miki, Murata
    • Journal Title

      Mod Rheumatol 14(4)

      Pages: 323-326

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3 : gene duplication is more prevalent in rheumatoid arthritis.2004

    • Author(s)
      Osawa K
    • Journal Title

      Genes Immun 5.6

      Pages: 439-443

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A case of central nervous system lupus in succession to lupus nephritis.2004

    • Author(s)
      Murata M
    • Journal Title

      Mod Rheumatol 14.4

      Pages: 323-326

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 関節リウマチと分子シャペロン-HSP90を介した滑膜細胞のシグナル伝達系-2004

    • Author(s)
      柱本照
    • Journal Title

      臨床リウマチ 16.3

      Pages: 181-187

    • Related Report
      2004 Annual Research Report
  • [Publications] KAWASAKI H: "Human weel kinase is directly transactivated by and increased in association with c-Fos/AP-1 : rheumatoid synovial cells overexpressing these genes go into aberrant mitosis"Oncogene. 22・44. 6839-6844 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiozawa S: "Fasciitis ; Whay is the significance of various forms?"J Clin Rheumatol. 9. 1-3 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashita T: "Enhanced insulin sensitivity in mice lacking ganglioside GM3"Proc Natl Acad Sci U S A. 100・6. 3445-3449 (2003)

    • Related Report
      2003 Annual Research Report

URL: 

Published: 2003-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi