| Project/Area Number |
10670131
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NISHI Shinzo Hokkaido Univ., Sch. Med., Pro., 医学部, 教授 (20001894)
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| Co-Investigator(Kenkyū-buntansha) |
NAKABYASHI Hidekazu Hokkaido Univ., Grad. Sch. Med., Inst., 医学部, 助手 (10033383)
SAKAI Masaharu Hokkaido Univ., Sch. Med., Asso. Pro., 医学部, 助教授 (50162269)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | α-fetoprotein / immunosuperssion / auto-imune doseases / T-cell / hepatocellular cacinoma / transgenic mice / 遺伝子 / 甲状腺炎 / Tリンパ球 / マイトジェン |
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| Research Abstract |
α-fetoprotein (AFP) is a serum protein in appreciable amounts in fetal but not in adult serum. However, serum AFP is frequently elevated in patients with hepatocellular carcinomas and yolk sac tumors. Numerous studies have suggested that immunomodulation may be one of the biological functions of AFP. To clarify the biological function of the AFP in vivo, we have established a transgenic mouse, which has a human AFP gene under the control of β-actin promoter. In this mouse, ubiquitous expression of AFP is observed. Using these mice, we have been analyzed experimental autoimmune diseases, such as arthritis, autoimmune thyroiditis and experimental encephalomyelitis. We have showed that development of all these experimental autoimmune diseases were significantly suppressed in AFP produced transgenic mice compared with wild mice. In vitro phytohemagglutinin response of splenocytes from transgenic mice was lower than that from wild mice. Significantly reduced numbers of CD4+, CD8+ thymocytes were found in the transgenic mice. These observations suggest that ubiquitously produced AFP modulate in vivo T cell development and/or T cell dependent immune responses. Now, we have constructed the targeting plasmid for establishment of the AFP gene disrupted mice.
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