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Establishment of animal model for Sjogren's syndrome and genetic analysis of the susceptibility loci

Research Project

Project/Area Number 11557154
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Surgical dentistry
Research InstitutionTohoku University

Principal Investigator

MORI Shiro  Tohoku University, Dental Hospital, Lecturer, 歯学部・附属病院, 講師 (80230069)

Co-Investigator(Kenkyū-buntansha) NOSE Masato  Ehime University, School of Medicine, Professor, 医学部, 教授 (70030913)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsSjogren's syndrome / sialadenitis / autoimmunediseases / animal model / microsatellite makers / genome analysis / polygene / susceptibility loci / 唾液線炎 / ループスモデルマウス / リンケージ解析
Research Abstract

To clarify the mode of inheritance of autoimmune sialadenitis and identify the susceptibility loci in Sjogren's syndrome, genome-recombinant mice that develop collagen disease involving sialadenitis in addition to polyarteritis, lupus nephritis, rheumatoid arthritis were prepared, and sialadenitis in individual mice was analyzed by histopathologic grading. The genomic DNA of these mice was examined by simple sequence-length polymorphism analysis, and the highly associated polymorphic microsatellite markers with sialadenitis were determined as sialadenitis susceptibility loci. Four susceptible gene loci recessively associated with sialadenitis were mapped on chromosomes 10,18,4, and 1, respectively. These loci manifested additive and hierarchical properties in the development of sialadenitis. The results indicate that sialadenitis in MRL/lpr mice is under the control of polygenic inheritance, possibly involving allelic polymorphism. On the other-hand, since it has been suggested that polygenic inheritance are easily influenced by extrinsic factors such as viral infection, influence on the manifestation of the collagen diseases by interferon regulatory factor-1 (IRF-1) which expression is induced by viral infection was also examined. For this purpose, IRF-1 transgene was inserted into a chromosome of an MRL/MpJ-lpr/lpr mouse, and a novel strain of transgenic mouse, MRL/Mn-IRF1-lpr/lpr mice were established. As a result, histopathological grading of sialadenitis of the transgenic mice was significantly increased while grading of other lesions such as polyarteritis, lupus nephritis, and rheumatoid arthritis was decreased. From these results, we conclude that manifestation of autoimmune lesions in mice of MRL strain are under the control of polygenic inheritance, and influenced by extrinsic factors such as IRF-1 expression.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Sakamoto, M., Miyazawa, M., Mori, S., Fujisawa, R.: "Anti-cytoplasmic autoantibodies reactive with epithelial cells of the salivary gland in sera from patients with Sjogren's syndrome : their disease and organ specificities"Journal of Oral Pathology and Medicine. 28. 20-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakatusuru, S., (+12), Mori, S., Nakamura, Y., Nose, M.: "Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice"Pathology International. 49. 974-982 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishihara, M., (+3), Mori, S., Nakatsuru, S., Nakamura, Y., Nose, M.: "Genetic basis of autoimmune sialoadenitis in MRL/lpr lupus mice : additive and hierarchical properties on polygenic inheritance"Arthritis and Rheumatisin. 42. 2616-2623 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wei-Min Qu, (+5), Mori, S., Nakamura, Y., (+3), Nose, M.: "Genetic dissection of vasculitis in MRL/lpr lupus mice : a novel susceptibility locus involving the CD72^c allele"Eur J Immunol. 30. 2027-2037 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nose, M., Terada, M., (+4), Mori, S., Nakatsuru, S.: "Genome analysis of collagen disease in MRL/lpr mice : polygenic inheritance resulting in the complex pathological manifestations"International Journal of Cardiology. 75. S53-S61 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kamogawa, J., (+4), Mori, S., (+3), Nakamura, Y., Nose, M.: "Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains"Arthritis and Rheumatism. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Maya Sakamoto, Masaaki Miyazawa, Shirp Mori, Ryuichi Fujisawa: "Anti-cytoplasmic autoantibodies reactive with epithelial cells of the salivary gland in sera from patients with Sjoren's syndrome: Their disease- and organ-specificities."J. Oral Pathol. Med.. 28. 20-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Syuichi Nakatsuru, Miho Terada, Miyuki Nishihara, Junji Kamogawa, Tatsuhiko Miyazaki, Wei-Min Qu, Koji Morimoto, Chie Yazawa, Hideki Ogasawara, Yoriko Abe, Keiko Fukui, Go Ichhien, Mitsuko R. Ito, Shiro Mori, Yusuke Nakamura, Masato Nose: "Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice."Pathol. Int.. 49(11). 974-982 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyuki Nishihara, Mino Terada, Junji Kamogawa, Yuichi Ohashi, Shiro Mori, Syuichi Nakatsuru, Yusuke Nakamura, Masato Nose: "Genetic basis of autoimmune sialoadenitis in MRL/lpr lupus mice: additive and hierarchical properties on polygenic inheritance."Arthritis Rheum. 42(12). 2616-2623 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wei-Min Qu, Tatsuhiko Miyazaki, Miho Terada, Ling-Min Lu, Miyuki Nishihara, Akihiro Yamada, Shiro Mori, Yusuke Nakamura, Hideaki Ogasawara, Chie Yazawa. Shuichi Nakatsuru, Masato Nose: "Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD 72 allele"Eur. J. Immunol.. 30. 2027-2037 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masato Nose, Miho Terada, Miyuki Nishihara, Junji Kamogawa, Tatsuhiko Miyazaki, Wei-Min Qu, Shiro Mori, Syuichi Nakatsuru: "Genome analysis of collagen disease in MRL/lpr mice: Polygenic inheritance resulting in the complex pathological manifestations."Int. J. Cardiol.. 75. S53-S61 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Junji Kamogawa, Miho Terada, Shinichi Mizuki, Miyuki Nishihara, Haruyasu Yamamoto, Shiro Mori, Yoriko Abe, Koji Morimoto, Syuichi Nakatsuru, Yusuke Nakamura, Masato Nose: "Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains."Arthritis Rheum. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kamogawa.J., (+4), Mori, S., (+3), Nakamura, Y., Nose, M.: "Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains"Arthritis and Rheumatism. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakatsura S,Terada M.Nishihara M.(+2) Mori S Nakamura Y.Nose M: "Genetic dissection of the complex pathological manifestation of collagen disease in MRL/lpr mice"Pathology International. 49(11). 974-982 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishihara M.Terada M.(+2).Mori S.Nakatsura S.Nakamura Y.Nose M: "Genetic basis of autoimmune sialoadenitis in MRL/lpr lupus mice : additive and hierarchical proprties on polygenic inheritance"Arthritis and Rheumatism. 42(12). 2616-2623 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wei-MinQ,Miyazaki T,(+4).Mori S.(+4).Nose M.: "Genetic dissection of vasculitis in MRL/lpr lupus mice : a novel susceptibility locus involving the CD72 allele"Eur J Immunol. 30. 2027-2037 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nose M.Terada M.Nishihara M.(+3) Mori S.Nakatsura S: "Genome analysis of collagen disease in MRL/lpr mice : polygenic inheritance resulting in the complex pathological manifestations"International Journal of Cardiology. 75. S53-S61 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakatsuru S.,Terada M.,Nishihara M.,(+10),Mori S.,Nakamura Y.,Nose M.: "Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice"Pathology International. 49(11). 974-982 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishihara M.,Terada M.,(+2),Mori S.,Nakatsuru S.,Nakamura Y.,Nose M.: "Genetic basis of autoimmune sialoadenitis in MRL/lpr lupus mice: additive and hierarchical properties on polygenic inheritance"Arthritis and Rheumatism. 42(12). 2616-2623 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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