| Project/Area Number |
11470125
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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 |
内科学一般
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| Research Institution | Tokai University |
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Principal Investigator |
KIMURA Minoru Tokai Univ. Sch. of Med. Professor, 医学部, 教授 (10146706)
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| Co-Investigator(Kenkyū-buntansha) |
IONKO Hidetosih Tokai Univ., Sch. Of Med., Professor, 医学部, 教授 (10101932)
SATO Masahiro Tokai Univ., Inst. Of Medical Scienses, Associate Professor, 総合医学研究所, 助教授 (30287099)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | human genome / genome anlaysis / susceptibility gene / Behcet's disease / Psoriasis Vulgaris / transgenic mouse / microsatellite / deisease model / ヒト疾患 / 尋常性乾鮮 / SNP / ベーテェット病 |
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| Research Abstract |
Based on our previous achievement that HLA region (spanning 1.8 Mb) positioned at the short arm of 6p21. 3 in the human chromosome 6 has already been sequenced with high accuracy, we attempted to identify candidate genes responsible for two human diseases (Bechet's disease [BA] and Psoriasis-[PA]) and create animal models for these two diseases. The following is the achievement we have performed in the past three years.
1. A region responsible for PA was confined to a region spanning 89 to 143 kb from the telomere side of HLA-C locus by genetic analyses. In this region, there were one known and 4 novel genes expressed in a skin. Sequencing of this region revealed that one of the 4 novel gene exhibited a significant polymorphism. This gene was termed "SEEK1" and found to overexpress in the skin suffered with PA.
2. For the candidate gene for BD, HLA-B gene itself or its neiboring MICA or MICB gene has been considered for the best candidate. However, recent genetic analysis revealed that HLA-B51 gene is the responsible gene for BD.
3. We produced several transgenic (Tg) lines carrying a 30-kb fragment containing SEEK1 gene. Further analysis of these lines is now underway.
4. We have already produced Tg lines carrying MICA or MICB gene, just prior to decision that HLA-B51 gene is the responsible gene for BD. These MICA or MICB Tg lines exhibited several abnormalities such as reduction in the nubmer of leukocytes and body weight, and hyperkeratosis in the skin, suggesting possible involvement of these genes in the pathogenesis of BD.
5. We also produced Tg lines carrying HLA-B51 and human b2-microglobulin genes and found that in these mice expression of HLA-B51 molecules on the cell surface was greatly elevated. Mice carrying human b2-microglobulin (b2m) and HLA-B51 genes, but lacking mouse b2m gene are now successfully produced using b2m-knock out mice.
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