| Project/Area Number |
15390607
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
MORI Shiro Tohoku University, Hospital, Lecturer, 病院, 講師 (80230069)
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| Co-Investigator(Kenkyū-buntansha) |
NOSE Masato Ehime University, School of Medicine, Professor, 医学部, 教授 (70030913)
ONO Masao Tohoku University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20302218)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | MRL / lpr / C3H / McH-lpr / lpr-RA1 / rpl / arthritis / arthropathy / animal model / microsatellite markers / 関節リウマチ / 関節炎 / モデル動物 / ゲノム解析 / 疾患感受性遺伝子 / MpJ-lpr / HeJ-lpr / MpJ-1pr / 1pr / HeJ-1pr |
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| Research Abstract |
To develop arthritis model in higher incidence, backcross generation mice, MRL/lpr x (MRL/lpr x C3H/lpr)F1, was prepared, and the mice developing severe arthritis were selected based on macroscopic findings of joint swelling and continued further intercrosses. From generation F54, the recombinant congenic strain of mice was designated McH-lpr/lpr-RA1 (McH/lpr-RA1). Arthritis in McH/lpr-RA1 mice developed earlier and in higher incidence compared with that in MRL/lpr mice, microscopically showing severe bone destruction with active resorption, resulting in ankylosis. Moreover, temporomandibular joint of McH/lpr-RA1 showed osteophyte formation. These results indicate that genomic recombination causes the remodeling of pathological phenotypes of arthritis. In addition, we recently found the spontaneous onset of arthropathy in the particular F_1 mice descended from two Fas-deficient strains of mice ; a mutant substrain of MRL/lpr (MRL/rpl) and C3H/lpr. To clear the histopathological charact
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erization and genetic interpretation for the unique inheritance mode of disease in this arthropathy model, MRL/rpl, C3H/lpr, (MRL/rpl x C3H/lpr)(MC)F_1, (C3H/lpr x MRL/rpl)(CM)F_1 and MCF_2 were bred and were analyzed. Incidence of microscopic arthropathy in the male and female MCF_1 groups was 100% and 19.4%, respectively. No incidence was observed in the parental strains, MRL/rpl and C3H/lpr, and CMF_1 mice. In the MCF_1 mice, the arthropathy mainly affected ankle joints and was histopathologically characterized by marked entheseal proliferation with chondrocytic differentiation and ossification in the ankle joints. An MRL/rpl-derived autosomal dominant susceptibility locus to the ankylosis onset was mapped in the distal of D7Mit68 (60 cM). The MCF_1 mice stably develop spontaneous ankylosing disorders in the ankle with male-predominance. The unique inheritance mode of ankylosis is possibly interpreted by the genetic interaction between the autosomal dominant locus and a Y-linked locus. Less
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