利用转基因斑马鱼研究LaminA/C对造血发育的影响及分子机制的研究

项目名称： 利用转基因斑马鱼研究LaminA/C对造血发育的影响及分子机制的研究

项目编号： No.31260284

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 舒莉萍

作者单位： 贵阳医学院

项目金额： 52万元

中文摘要： 核纤层蛋白是维持核膜正常形态的主要骨架蛋白，在提供染色体锚定位点以及在核周期性的解体和重组装过程中发挥着重要作用。其中核纤层蛋白LMNA（laminA/C）异常可以引起骨骼肌、心肌、脂肪和神经等各个组织的严重或恶性病变，也可以引起血液系统的恶性疾病。但是其对造血发育影响的研究，以及发病机制及分子机制的研究罕见报道。因此，本课题利用斑马鱼独特生物学和遗传学优势，即造血调控网络与人类高度保守、胚胎体外发育而且通体透明、可直接动态监测造血发育全过程，便于进行细胞生物学研究等特点，遂利用可示踪的各造血祖细胞转基因斑马鱼模型，在斑马鱼体内分别下调laminA/C基因；进一步探讨laminA/C在造血发育过程中的功能，阐明其可能的机制，以期深入对核纤层蛋白laminA/C的认识，并为人类疾病斑马鱼模型的构建和研究提供参考。

中文关键词： 斑马鱼；laminA/C；基因下调；；

英文摘要： The LMNA gene produces A-type lamins, which provides a scaffold for the organization of nuclear to support the normal form of the nuclear envelope, and has been implicated in the maintenance of nuclear architecture and chromatin structure. Despite many studies demonstrating the mutations of laminA/C are associated with a variety of malignant hematologic diseases, affected skeletal muscle, cardiac muscle and fat to nurve and so on.And some changes in the expression of LMNA are observed in the malignant hematologic diseases,but its hematopoiesis developmental role as well as the molecular mechanisms involved are still poorly understood.Zebrafish are being increasingly used as a model organism to study Hematopoiesis. This genetically tractable model has many appealing features, such as zebrafish eggs are fertilized externally and are transparent to readily available for observation the whole progress of the hematopoiesis. We suggest to use antisense morpholino oligo to knockdown laminA/C expression in the generated transgenic zebrafish lines with fluorescent protein-tagged Hematopoietic transcription factor,tracing the cell, assessed the blood cell circulation throughout development, investigate the LaminA/C function in the hematopoiesis. and its the molecular mechanisms involved . It will give help

英文关键词： zebrafish；laminA/C；gene knock-down；；