用斑马鱼和小鼠研究核仁基因nom1突变后造成胰腺发育缺陷的作用机制

项目名称： 用斑马鱼和小鼠研究核仁基因nom1突变后造成胰腺发育缺陷的作用机制

项目编号： No.31271550

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： 仲寒冰

作者单位： 北京大学

项目金额： 80万元

中文摘要： 申请人在前期工作中筛选到了一个斑马鱼胰腺发育缺陷突变体dc5，其胰腺内分泌腺增大，约为野生型的2倍，外分泌腺减小，约为野生型的1/6。用定位克隆方法找到了突变的基因是nom1。初步的表达谱分析显示nom1是母源基因，在斑马鱼胚胎中泛表达。Nom1于2005年在人中首先被克隆，至今只有3篇功能研究的文章。已知nom1定位于核仁区，跟eIF4A1、eIF4A2、eIF4A3和PP1γ等有直接的物理接触。在HEK293T细胞中用siRNA敲低nom1造成18S rRNA产率下降。这些研究结果不能把nom1跟胰腺发育联系起来，因此申请人计划研究nom1功能缺失后造成胰腺发育缺陷的作用机理，回答下面的问题：1. nom1是通过跟哪些基因相互作用来调控胰腺发育，怎样整合到已知的调控网络中？2.nom1作为泛表达的持家基因，通过什么方式来特异性地影响胰腺发育？而对其它的器官没有显著影响？

中文关键词： nom1；胰腺；肝脏；斑马鱼；小鼠

英文摘要： In a genetic screening, a pancreas mutant dc5 was identified. In dc5 mutant, the endocrine pancreas increases to about two folds of wild type group, and the exocrine pancreas reduces to about 1/6 of wild type group.The mutated gene, nom1, was cloned by positional cloning approach.In situ hybridization with nom1 antisense RNA probe showed that nom1 is ubquintiously expressed in embryo and it's a maternal gene. Up to date, there are only 3 published papers of nom1 functional study. Nom1 was first cloned in human in 2005. In cultured cell, nom1 is localized in nucleolus and has physical interactions with eIF4A1, eIF4A2, eIF4A3 and PP1γ. In HEK293T cell, knockdown of nom1 by siRNA caused decrease of the formation rate of 18S rRNA. These findings can not link nom1 to pancreas development. Therefore, we plan to investigate the role of nom1 in pancreas development, and answer two main questions: 1. which genes does nom1 interact with to regulate the development of pancreas? 2. As a ubiquitiously expressed housekeeping gene, how does nom1 seletively regulate pancreas, but not cause severe overall defect? Two more cases of housekeeping gene regulating a certain kind of cell were reported previously, RPS19 regulates erythropoiesis and seryl-tRNA synthetase regulates angiogenesis. So we speculate that there might be some u

英文关键词： nom1；pancreas；liver；zebrafish；mouse