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1993 Fiscal Year Final Research Report Summary

Studies on background genes aggravating lpr^<cg>-induced nephritis and complementation between lpr^<cg> and gld genes

Research Project

Project/Area Number 04454185
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

MATSUZAWA Akio  Associate Professor Institute of Medical Science, University of Tokyo, 医科学研究所, 助教授 (50012745)

Co-Investigator(Kenkyū-buntansha) WATANABE Tomomasa  Section Head Institute of Developmental Research, Aichi Prefecture Colony, 発達障害研究所, 室長 (10100174)
KATAGIRI Takuya  Assistant Researcher Institute of Medical Science, University of Tokyo, 医科学研究所, 助手 (70126100)
KIMURA Mikio  Assistant Researcher Institute of Medical Science, University of Tokyo, 医科学研究所, 助手 (90114462)
Project Period (FY) 1992 – 1993
KeywordsLpr^<cg> gene / Gld gene / Autoimmunity / MRL mice / Nephritis / Complementation / Lymphadenopathy / Homing
Research Abstract

Linkage tests were conducted using the intersubspecific backcross of (CBA-lpr^<cg> x MOL-MIT)F_1 x CBA-lpr^<cg> and led to the conclusion that the lpr^<cg> gene locates between Ly-44 and Tdt on chromosome 19 at the distances : centromere-Ly-44 -(17.0 cM)-lpr^<cg>-(5.3 cM)-Tdt-telomere.
Both homozygous and heterozygous lpr^<cg> gene induced more severe autoimmune syndromes, nephritis and vasculitis on the MRL than the CBA background. To analyze the effects of background genes, backcross offspring were examined from the interspecific cross of (MRL-lpr x CAST/Ei)F_1 x MRL-lpr. The profound effects of background genes on the extent of nephritis, lymphadenopathy and anti-DNA antibody were demonstrated. Of major note, this study suggested the identification of chromosomal positions for genes that modify nephritis. Analysis of the backcross mice for markers covering most of the mouse genome suggest that over 50% of the variance in renal disease is attributable to quantitative trait loci on mouse chromosomes 7 and 12. These loci may also participate in aggravation of lpr^<cg>-induced nephritis.
Simultaneous bone marrow (BM) and lymph node (LN) transplantation into (CBA x C3H)F_1 (F_1) mice was performed in various genotype combinations. Grafted C3H-lpr/lpr and CBA-lpr^<cg> LN swelled but +/+ and C3H-gld/gld LN strophied in recipients of lpr/lpr or lpr^<cg>/lpr^<cg> BM.All LN of these genotypes swelled in recipients of gld/gld BM.Thus, lpr and lpr^<cg> are phenotypically different from gld in the interaction of BM-derived double negative (DN) T cells and +/+ LN.Lymphadenopathy induced by the cooperation between lpr^<cg> and gld was confirmed to be lpr but not of gld phenotype by a similar method.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Ogata,J.: "Distinctive expression of lpr^<cg> in the heterozygous state on different genetic backgrounds" Cellular Immunology. 148. 91-102 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,T.: "A new allele at the lpr gene on mouse chromosome 19 expresses properties different from the original recessive mutatiom" Mammalian Genome. 4. 346-347 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogasawara,J.: "Lethal effect of the anti-Fas antibody in mice" Nature. 364. 806-809 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano,H.: "Nonspecific augmentation of lymph node T cells and I-E-independent selective deletion of Vb14^+ T cells by Mtv-2 in the DDD mouse" European Journal of Immunology. 23. 2434-2439 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,M.: "Autoimmunity in mice bearing lpr^<cg>:a novel mutant gene" International Review of Immunology. (未定)(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanabuchi,S.: "Fas and its ligand in a general mechanism of T cell-mediated cytotoxicity" Proceedings of National Academy of Science. (未定)(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuzawa,A.: "Lymphadenopathy induced by the cooperation between lpr^<cg> and gld genes is of lpr but not of gld phenotype" European Journal of Immunology. (未定)(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogata, Y., Kimura, M., Shimada, K., Wakabayashi, T., Onoda, H., Katagiri, T.and Matsuzawa, A.: "Distinctive expression of lpr^<cg> in the heterozygous state on different backgrounds." Cellular Immunology. 148. 91-102 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, T., Sakai, Y., Hanai, A., Masaki, S., Ohno, . K., Miyawaki, S.and Matsuzawa, A.: "A new allele at the lpr gene on chromosome 19 expresses properties different from the original recessive mutation." Mammaliam Genome. 4. 346-347 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogasawara, J., Fukunaga, R.W-., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T.and Nagata, S.: "Lethal effect of the anti-Fas antibody in mice." Nature. 364. 806-809 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano, H., Yoshimoto, T., Kakiuchi, T.and Matsuzawa, A.: "Nonspecific augmentation of lymph node T cells and I-E-independent selective deletion of Vb14^+ T cells by Mtv-2 in the DDD mouse." European Journal of Immunology. 23. 2434-2439 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, M.and Matsuzawa. A.: "Autoimmunity in mice bearing lpr^<cg> : a novel mutant gene." International Review of Immunology. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanabuchi, S., Koyanagi, M., Kawasaki, A., Shinohara, N., Matsuzawa, A., Nishimura, Y., Kobayashi, Y., Yonehara, S., Yagita, H.and Okumura, K.: "Fas and its ligand in a general mechanism of T cell-mediated cytotoxicity." Proceedings of National Academy of Science. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuzawa, A., Katagiri, T., Ogata, Y., Kominami, R.and Kimura, M.: "Lymphadenopathy induced by the cooperation between lpr^<cg> and gld genes is of lpr but not of gld phenotype." European Journal of Immunology. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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