High-throughput gene disruption in zebrafish using retroviral integration

摘要 斑马鱼已被广泛用作研究脊椎动物发育和遗传学的模式动物。这很好 证实了对斑马鱼基因的遗传研究可以提供对保守的 研究脊椎动物的基因，因此有助于更好地了解人类疾病和健康。和斑马鱼一起 基因组测序计划即将完成，人们非常希望所有由 测序还将携带一种随时可用于基因功能研究的突变。为了实现这个目标，我们 开发了使用前病毒插入与高吞吐量相结合的高效、简化的平台 测序和作图技术，基本上诱变所有可识别的候选基因 斑马鱼基因组。在这个项目中，我们建议通过以下方式向公众研究社区提供基因工具 构建斑马鱼品系文库，其中约12,000个斑马鱼基因已被打乱 通过逆转录病毒植入。所有产生的资源都将提供给社区，只需最少的 出版前成本。

Abstract Zebrafish has been widely used as a model animal to study vertebrate development and genetics. It is well established that genetic studies of zebrafish genes can provide insights into the function of the conserved vertebrate genes and therefore lead to better understanding of human diseases and health. With the zebrafish genome sequencing project nearly completed, it is highly desirable that all of the genes predicated by sequencing will also carry an mutation that readily available for gene function studies. Towards this goal, we have developed an efficient and streamlined platform using proviral insertions coupled with high-throughput sequencing and mapping technologies to mutagenize essentially all of the identifiable candidate genes in zebrafish genome. In this project we propose to provide genetic tools to the public research community by constructing a library of zebrafish strains in which approximately 12,000 zebrafish genes have been disrupted with a retrovirus insertion. All the resources generated will be made available to the community with a minimal cost before publication.