Identification of genes important in myeloid and haemopoietic development by genetic screening in zebrafish

通过斑马鱼遗传筛选鉴定对骨髓和造血发育重要的基因

• 批准号: nhmrc : 234708
• 负责人: Dr Judith Layton
• 金额: $ 28.36万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/identification-genes-important-screening-zebrafish/81317
• 关键词: Identification; genes; important; myeloid; haemopoietic

Zebrafish have emerged as a powerful experimental model in developmental genetics. Their favourable attributes include their reproductive biology, the optical clarity of embryos, and the accessibility of embryos for experimental procedures. Previous studies overseas have recovered over 1500 strains of zebrafish with inherited diseases due to induced mutations in about 500 genes. Many of these zebrafish have abnormalities of unexpected precision and are leading to new genes with novel specialized functions. About 50 mutant zebrafish strains exist in which red blood cell development is perturbed - this was easily recognized because the transparency of embryos enabled lack of blood be easily seen. Our new studies aim primarily to recover mutant zebrafish with disorders of white blood cell formation. We have identified methods to recognize failure of white blood cell formation in zebrafish, and will employ these methods to look for inherited disorders that specifically affect white blood cell development in a process called genetic screening. Fish with different sets of randomly mutated genes will be systematically screened to identify those with abnormal white blood cell development. We have tested our approach and identified several mutants affecting white blood cell development. Once these new strains of fish are identified, we will find the genetic lesion responsible for the abnormality in several of the most interesting strains by gene mapping and positional cloning. Hence, the mutant zebrafish identified in the screen will eventually lead to the discovery of new genes important in white blood cell growth and development. The fish themselves will provide insights into the causes of congenital diseases of white blood cells. Since many genes involved in early development are also important in cancer, we believe that newly identified genes will also help understand the causes of abnormal growth of white blood cells in leukaemia.

斑马鱼已成为发育遗传学领域强大的实验模型。它们的有利属性包括生殖生物学、胚胎的光学透明度以及胚胎用于实验程序的可及性。此前海外研究已发现超过1500种斑马鱼因约500个基因发生突变而患有遗传性疾病。许多斑马鱼具有意想不到的精确异常，并导致产生具有新颖专门功能的新基因。大约有 50 种突变斑马鱼品系的红细胞发育受到干扰，这一点很容易被识别，因为胚胎的透明性使得血液的缺乏很容易被发现。我们的新研究主要旨在恢复患有白细胞形成障碍的突变斑马鱼。我们已经确定了识别斑马鱼白细胞形成失败的方法，并将利用这些方法在称为遗传筛查的过程中寻找专门影响白细胞发育的遗传性疾病。将系统地筛选具有不同组随机突变基因的鱼，以识别那些白细胞发育异常的鱼。我们测试了我们的方法并鉴定了几种影响白细胞发育的突变体。一旦鉴定出这些新的鱼类品系，我们将通过基因作图和定位克隆找到导致几个最有趣的品系异常的遗传病变。因此，筛选中发现的突变斑马鱼最终将导致发现对白细胞生长和发育很重要的新基因。这些鱼本身将为白细胞先天性疾病的病因提供见解。由于许多参与早期发育的基因在癌症中也很重要，因此我们相信新发现的基因也将有助于了解白血病中白细胞异常生长的原因。