| 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)
関川 巌 順天堂大学, 医学部, 助手 (80179332)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Autoimmunity / SLE / MHC / TCR / congenic mouse / transgenic mouse / New Zealand mouse / New Aealandマウス / 全身性エリテマト-デス / Transgenicマウス / New Zealandマウス / 全身性エリテマトーデス / クラスII抗原 / コンジェニックマウス / トランスジェニックマウス / 自己免疫遺伝子 |
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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
… More
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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