1989 Fiscal Year Final Research Report Summary
Studies of autoimmune disease using mice with genetic recombination
| Project/Area Number |
62480144
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Juntendo University |
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Principal Investigator |
SHIRAI Toshikazu Juntendo Univ., Pathology, Professor, 医学部, 教授 (30115860)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Hiroyuki 順天堂大学, 医学部, 助手 (60189313)
OKADA Takashi 順天堂大学, 医学部, 助手 (20185440)
TANNO Masataka Juntendo Univ., Pathology, instructor, 医学部, 助手 (50171913)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Autoimmunity / SLE / MHC / TCR / congenic mouse / transgenic mouse / New Zealand mouse / New Aealandマウス |
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| Research Abstract |
The multi-gene effect is responsible for the development of severe autoimmune disease in (NZB X NZW)Fl mice, resembling human systemic lupus erythematosus. Using H-2 congenic mouse strains, we demonstrated that the beterozygosity of the H-2^d from NZB and H-2^z from NZW mouse is required for the development of IgG anti-DNA antibodies and severe lupus nephritis in these mice, and have proposed that the Fl unique hybrid class ll molecules may act as a restriction element. This idea was supported by our finding of progeny studies in which a locus or a cluster of loci linked to T cell receptor beta chain gene complex of the NZW strain in combination with H-2^d/H-2^Z heterozygosity is associated with the production of IgG anti-DNA antibodies in these mice. Together with our previous finding of the strict CD4^+ T cell dependency of IgG anti-DNA antibody production in (NZB X NZW)Fl mice, it appears that the interaction between the unique structures of the T cell receptors and the Fl unique hy
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brid class II molecules is preferable for IgG anti-DNA antibody synthesis. We then analyzed the polymorphism of class II genes of NZB and NZW strains by the nucleotide sequence analysis, and found that NZW(H-2^z) Ebeta is identical to that of BlOPL(H-2^u) except for two N-terminal two amino acid differences (Arg^1 Gly^2 for Ebeta^u and Val^1 Arg^2 for Ebeta^z). The second exon sequences of NZW Abeta, Aalpha, Ealpha genes were shown to be identical to those of H-2^u. MHC class II polymorphism of NZB mice appeared to be identical to that of Balb/c mice(H-2^d). Analysis suggested that unique polymorphism in Ealpha alpha 1 domain of NZW mice which is so far found only in u and z haplotypes may contribute to the formation of Fl unique hybrid E molecule which should be formed in H-2^d/H-2^z heterozygosity. To investigate the possible roles of these Fl unique hybrid class II molecule on autoimmuno disease of (NZB X NZW) Fl mice. studies are under way using several strains of class II transgenic. H-2 congenic mice. Less
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[Publications] Sekigawa,I.,Okada,T.,Noguchi,K.,Ueda,G.,Hirose,S.,Sato,H.&Shirai,T.: "Class-specific regulation of anti-DANA antibody syntesis and the age-associated changes in(NZB X NZW)F1 hybrid mice." J.Immunol.138. 2890-2895 (1987)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yanagi,Y.,Tada,T.,Hirose,S.,Nagasawa,R.,Shirai,T.& Tak,T.W.: "New Horizons in Animal Models for Autoimmune Disease" Academi press(Eds.kyogoku,M.et al.), 115-120 (1987)
Description
「研究成果報告書概要(和文)」より
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[Publications] Sekigawa, I., Okada, T., Noguchi, K., Ueda, G., Hirose, S., Sato, H. & Shirai, T.: "Class-specific regulation of anti-DNA antibody synthesis and the age-associated changes in (NZB X NZW)Fl hybrid mice." J. Immunol. 138: 2890-2895, 1987.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yanagi, Y. Tada, T., Hirose, S., Nagasawa, R., Shirai, T. & Mak, T.W.: "T cell receptor gene deletion and autoimmunity in (NZE X NZW)Fl mice." New Horizons in Animal Models for Autoimmune Disease.(Eds. Kyogoku, M. et al.) Academic Press, 115-120, 1987.
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「研究成果報告書概要(欧文)」より
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[Publications] Shirai, T., Hirose, S., Okada, T. & Nishimura, H.: "Immunology and immunopathology of the autoimmune disease of NZB and related mouse strains." Genetically Based Immunological Disorders in Inbred Mice. (Eds. Rihove, E.B. et al.) CRC Press, Inc., N.W. Boca Raton, Fla.
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「研究成果報告書概要(欧文)」より
