1995 Fiscal Year Final Research Report Summary
Elucidation of properties and mechanism of development of autoimmune diseases in new congenic MRL/MpJ-lprcg/lprcg mice
| Project/Area Number |
06454190
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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 | The University of Tokyo |
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Principal Investigator |
MATSUZAWA Akio The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (50012745)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Tomomasa The Hokkaido University, Department of Veterinary Science, Professor, 獣医学部, 教授 (10100174)
WAKABAYASHI Tomo The University of Tokyo, Institute of Medical Science, Lecturer, 医科学研究所, 講師 (90092379)
KIMURA Mikio The University of Tokyo, Institute of Medical Science, Clinical Associate, 医科学研究所, 助手 (90114462)
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| Project Period (FY) |
1994 – 1995
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| Keywords | mouse model / lpr^<cg> gene / MRL background / autoimmunity / congenic / gromeluronephritis / artiritis / lymphadenopathy |
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| Research Abstract |
The novel lymphoproliferative and autoimmune lpr^<cg> gene, which we discovered in the CBA/KIJms (CBA) mice, was transferred onto the MRL/MpJ (MRL) background by 12 backcrosses. The resulting congenic MRL-lpr^<cg>/lpr^<cg> mice developed lymphoproliferative disease characterized by expansion of CD4-8-, Thy-1+, B220+ lymphoid cells (DN T cells). The histology of the kidney revealed that MRL-lpr^<cg>/lpr^<cg> mice developed glomerulonephritis indistinguishable from that in MRL-lpr/lpr although its frequency was slightly lower in the former. Glomerular immune complex deposition was almost the same in MRL-lpr^<cg>/lpr^<cg> and MRL-lpr/lpr mice. The levels of serum Ig, circulating immune complexes and autoantibodies in MRL-lpr^<cg>/lpr^<cg> were comparable to or even higher than those in MRL-lpr/lpr. Comparison between MRL-lpr^<cg>/lpr^<cg> with glomerulonephritis and CBA-lpr^<cg>/lpr^<cg> without it evidenced that the IgM-to-IgG class switch in class-specific autoantibody responses and serum Ig levels were enhanced in MRL-lpr^<cg>/lpr^<cg> as in MRL-lpr/lpr, Moreover, the function of the heterozygous lpr was investigated. MRL-lpr^<cg>/+ mice had significantly larger lymph nodes and spleens free from accumulation of anomalous DN T cells. Noticeably, the incidence and severity of gromeluronephritis were similar in MRL-lpr^<cg>/+ and -lpr^<cg>/lpr^<cg>, suggestive of no involvement of DN T cells in renal disease. These results taken together indicate that the lpr^<cg> functions through the same mehanism as lpr in induction of glomerulonephritis and serological abnormalities on the MRL background as expected from the allelism between both mutant genes and that the newly established conenic MRL-lpr^<cg>/lpr^<cg> mouse will provide a unique model for reserach into autoimmunity in mice.
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[Publications] Chu, J.L., Ramos, P., Rosendorff, A., Nikolic-Zugic, J., Lacy, E., Matsuzawa, A.and Elkon, K.B.: "Massive upregulation of the Fas ligand in lpr and gld mice : Implications for Fas regulation and the graft-versus-host disease-like wasting syndrome." J.Exp, Med.181. 393-398 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Suzuki, A., Enari, M., Eguchi, Y., Matsuzawa, A., Nagata, S., Tsujimoto, Y.and Iguchi, T.: "Involvement of Fas in regression of vaginal epithelia after ovariectomy and during an estrus cycle." EMBO J.(in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miez, M.A., Itoh, T., Cui, J.Q., Makino, Y., Tsuchida, K., Koike, T., Shiral, H., Yagita, H., Mtsuzawa A., Koyasu, S., Koseki, H.and Taniguchi, T.: "The selective reduction of V 14+ NK T cells preceding disease development in autoimmuneprone mice." J.Ex.Med. (in press).
Description
「研究成果報告書概要(欧文)」より
