利用斑马鱼cebpα突变体分析髓系造血调控机制并建立白血病疾病模型的研究

项目名称： 利用斑马鱼cebpα突变体分析髓系造血调控机制并建立白血病疾病模型的研究

项目编号： No.31271564

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 廖旺军

作者单位： 南方医科大学

项目金额： 75万元

中文摘要： 转录因子Cebpα在鼠胎儿及成年髓系造血中发挥着重要作用，其功能下降或缺失与人类髓系急性白血病密切相关。 我们的前期工作获得一个斑马鱼突变体，其早期髓系造血被阻断，导致髓系细胞（巨细胞系和粒细胞系）的缺失。基因定位显示突变基因为cebpα，突变体命名为cebpαsmu6。 本项目拟分析Cebpα在髓系造血中的作用并通过基因修饰cebpαsmu6突变体成鱼建立急性髓系白血病（AML）斑马鱼疾病模型，从而进一步研究Cebpα与另外两个已知髓系转录因子Pu.1和Runx1之间的相互关系，以便解释髓系发育和急性髓系白血的基因调控网络并可望提供一个治疗AML药物筛选的疾病模型。

中文关键词： cebpa；斑马鱼；髓系造血；；

英文摘要： Myeloid cells are central cellular components of blood system and essential regulators for the host defense, embryo/organo-genesis, and tissue regeneration. In vertebrates, myeloid cells are classified into two major lineages: granulocytic and monocytic lineages. Granulocytic lineage consists of neutrophils, eosinophils, basophils, and mast cells; and they are the key effectors of generating innate immunity. On the other hand, monocytic lineage, which includes the circulating monocytes and tissue-resident macrophages, plays crucial roles not only in inflammatory response but also actively participates in embryo/organo-genesis, tissue homeostasis, and tissue regeneration. The development of myeloid cells is tightly controlled and irregularities in their development are closely associated with the onset and progression of a variety of human disorders including myeloid leukemia. Studies have shown that myeloid cell development is predominantly governed by transcription factors, and mutations in those key regulators are attributed to the occurrence of myeloid leukemia in human patients. With its several unique advantages, zebrafish have emerged as an excellent model organism for the study of vertebrate development and human disorders and for drug screening. We recently isolated a myeloid-defective zebrafish mutant,

英文关键词： cebpa；zebrafish；myeloid haemopoiesis；；