| 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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