zkscan3基因新功能的解析

项目名称： zkscan3基因新功能的解析

项目编号： No.31471283

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 杨林

作者单位： 苏州大学

项目金额： 85万元

中文摘要： ZKSCAN3基因是一个具有锌指结构的转录因子，我们在前期发表的工作中证实其调控着重要的基因表达程序，在直肠癌、前列腺癌、骨髓瘤等的发展、转移和病理发生过程中，以及细胞自噬调控中发挥着重要的作用。但是，其正常生理条件下的生物学功能仍然大量未知。我们在国际上首次构建了zkscan3基因小鼠敲除模型，并在前期工作中发现zkscan3基因可能是一个B细胞功能的负调控因子，对机体的体液免疫应答起着关键的平衡作用。为了检验这一假设，我们将系统分析小鼠模型中体液免疫和细胞免疫的应答、B细胞的发育与成熟，并深入研究zkscan3基因对体液免疫应答和B细胞发育作用的分子机理，最终阐明zkscan3基因的主要生理学功能。

中文关键词： zkscan3基因；敲除小鼠；细胞分化；B淋巴细胞；转录调控

英文摘要： Previous studies from our group originally focusing on colorectal carcinoma, prostate cancer, and multiple myeloma determined that zinc finger with KRAB and SCAN domains 3 (ZKSCAN3), a novel zinc-finger transcription factor, coordinated a gene expression program and was an important driver for tumor development, migration, and pathogenesis, as well as autophagy regulation. However, the biological role of ZKSCAN3 gene under normal physiological condition remains largely unknown. We established a zkscan3 gene knock-out mouse model which has not been reported yet, and found that zkscan3 gene may be a negative regulator for B cell function, which may play a critical role in keeping homeostasis of humoral immune response. To verify this central hypothesis, we will systematically analyze the mouse model for its humoral responses with antigen stimulation, development and maturation of B cells. Furthermore, we will determine the molecular mechanism how zkscan3 gene regulates the humoral response and B cell development, and finally understand the major physiological role of zkscan3 gene.

英文关键词： zkscan3 gene;knock-out mouse;cell differentiation;B lymphocyte;transcriptional regulation