1994 Fiscal Year Final Research Report Summary
Analysis of the genes determining the susceptibility to autoimmune disease
| Project/Area Number |
05454186
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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 | Mie University (1994)
The Institute of Physical and Chemical Research (1993) |
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Principal Investigator |
SAKAKURA Teruyo Mie University Faculty of Medicine Professor, 医学部, 教授 (80073120)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Autoimmune disease / Gene mapping / Disease susceptibility gene |
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| Research Abstract |
To investigate the role of host genetic factors in the development of organ-specific autoimmune diseases, we have analyzed the genetic factors determining the susceptibility and/or phenotype of autoimmune diseases in the TCRalphaEH transgenic mice. This model spontaneously develops various organ-specific autoimmune diseases depending on the mouse strains introduced with the transgene. BALB/c and A/J mice, for example, predominantly develop autoimmune gastritis or oophoritis, respecively. Use of MHC congenic mice revealed a significant contribution of MHC to susceptibility to oophoritis : in contrast to A/J (H-2a), the A.By strain (H-2b) was resistant to oophoritis. A predominant role of non-MHC gene (s) was suggested for gastritis : BALB/c (H-2d), BALB.K (H-2k), and BALB.B (H-2b) were all susceptible to gastritis, whereas B10.D2 (H-2d) was resistant. Mapping of the susceptibility genes by the microsattelite mapping method revealed a gene on chromosome 8 contributing to gastritis susceptibility, and genes on chromosome 12 and 14 for the susceptibility to gastritis/oophoritis. An oophoritis-susceptibility gene on chromosome 17 near MHC locus was also confirmed by this mapping method. Further fine mapping and identification of these genes will contribute to our underdtanding of the pathogenetic mechanism of autoimmune disease and developing ways to prevent it.
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