| Project/Area Number |
10480172
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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 |
Functional biochemistry
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
HOMMA Yoshimi Fukushima Medical University School of Medicine, Department of Biomolecular Science, Professor, 医学部, 教授 (60192324)
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| Co-Investigator(Kenkyū-buntansha) |
KABUYAMA Yukihito Fukushima Medical University School of Medicine, research associate, 医学部, 助手 (20285042)
SEKIMATA Masayuki Fukushima Medical University School of Medicine, Lecturer, 医学部, 講師 (80250190)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | intracellular signaling / inositol phospholipid / phospholipase C / genome / homologous recombination / ontogenesis / 難治性潰瘍 / 相同組換え / ホモローガスリコンビネーション |
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| Research Abstract |
Phospholipase C (PLC) hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP_2) to generate inositol-1,4,5-trisphosphate (IP_3) and diacylglycerol (DAG), and this catalytic activity is controlled upon receptor activation. It is well understood that these two products, IP_3 and DAG, mediate the calcium release from intracellular stores and protein kinase C activation. Among PLC isoforms, this study focused on biological function of PLC-γ2, Mice with loss of PLC-γ2 function were produced using two different gene knockout strategies. Following results were obtained from this research project.
1) Using gene-targeting approach, mice heterogeneously harboring PLC-γ2 gene of which a catalytic X region was replaced by neo, were successfully produced. The homozygous mice, however, were embryonic lethal and died at 〜E8.5.
2) The PLC-γ2 gene was inducibly ablated by using IFN-regulated Cre recombinase. Mice with neonatally induced loss of PLC-γ2 function displayed reduced members of mature conventional B cells and peritoneal B l cells and defective responses in vitro to BCR stimulation and in vivo to immunization with thymusindependent type-II Ags. In contrast, T cell development and TCR-mediated proliferation were normal. These results indicate that PLC-γ2 is a critical component of BCR signaling pathways and is required to promote B cell development.
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