利用斑马鱼模型研究TRIM45基因在血祖细胞形成与分化中的作用

项目名称： 利用斑马鱼模型研究TRIM45基因在血祖细胞形成与分化中的作用

项目编号： No.31272396

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： 王跃群

作者单位： 湖南师范大学

项目金额： 79万元

中文摘要： 申请人克隆了一个造血相关侯选基因TRIM45，其编码蛋白属于具有三元模体的TRIM家族，此类蛋白在器官早期造血过程中发挥重要的作用。前期研究结果提示TRIM45在胚胎早期发育阶段可能与血祖细胞形成和分化的调控相关。本项目拟采用斑马鱼为模型研究该基因在血液发育的生物学功能、探讨其调控的信号途径：1）利用原位杂交等技术研究TRIM45基因在胚胎发育阶段的时空表达模式；2）利用Morpholinos反义寡核酸阻断翻译和mRNA拯救技术鉴定TRIM45与血祖细胞分化的关系；3）建立斑马鱼基因敲除和转基因动物模型，鉴定TRIM45在血祖细胞形成和分化中的功能；4)结合细胞模型探讨TRIM45在血祖细胞形成和分化中的分子调控信号途径。通过对造血过程中关键调节因子的研究有利于揭示造血作用的分子机制，完善调控信号途径，可能为相关疾病的治疗提供理论基础。

中文关键词： TRIM45；血祖细胞；造血干细胞；分化；斑马鱼

英文摘要： We have cloned a potential hematopoiesis related gene named TRIM45, and the protein product of this gene belongs to tripartite motif(TRIM) family. Some of TRIM family members might play an important role in regulating hematopoiesis in animal models. We have got some evidence supporting TRIM45 might play a role in regulating the formation and differentiation of hemangioblast during the early stage of embryo development. Using zebrafish as a animal model, this studies will focus on the the the biology function of TRIM45 on hematopoiesis and the potential signal pathway. 1）Using the method of in situ hybridization to study the spatiotemporal model of TRIM45. 2）Combining of Morpholinos oligos to knockdown and mRNA rescue to study the relationship between TRIM45 and differentiation of hemangioblast；3）Constraction of knockout and transgene zebrafish model to study the potential role the TRIM45 in regulating the formation and differentiation of hemangioblast；4) Combining the study on cell lines to understand the molecular signal pathway during the formation and differentiation of hemangioblast. Identification of key regulators in hematopoiesis might be of significance in clarify the molecular mechanisms underlying each process, build up the regulation signal pathway, and provide appropriate candidates for clinical trea

英文关键词： TRIM45；hemangioblast；hematopoietic stem cell；differentiation；zerbrafish