High-throughput gene disruption in zebrafish using retroviral integration

使用逆转录病毒整合对斑马鱼进行高通量基因破坏

• 批准号: 8141938
• 负责人: Shuo Lin
• 金额: $ 32.83万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141938
• 关键词: Address; Animal Model; Archives; Candidate Disease Gene; Communities; Coupled; Cryopreservation; Custom; Data; Databases; Development; Embryo; Event; Exons; Fishes; Freezing; Genbank; Generations; Genes; Genetic; Genome; Genomics; Goals; Health; Inbreeding; Introns; Knockout Mice; Lead; Libraries; Link; Location; Maps; Mediating; Messenger RNA; Mutagenesis; Mutate; Mutation; Partner in relationship; Probability; Protocols documentation; Publications; Recovery; Research; Resources; Retroviridae; Sampling; Services; Site; Technology; Transcript; Transgenic Organisms; Work; Zebrafish; cost; design; gene function; genome database; genome sequencing; human disease; insight; interest; male; mutant; novel therapeutic intervention; offspring; research study; sperm cell; success; tool; vertebrate genome; zebrafish genome

DESCRIPTION (provided by applicant): 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 a 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. PUBLIC HEALTH RELEVANCE: Zebrafish is a popular vertebrate model organism for studying development and human diseases and we use state of the art technologies to generate mutations in most of zebrafish genes. Since these genes are highly conserved our studies will provide valuable information for understanding human diseases and assisting design of novel therapeutic approaches.

描述（由申请人提供）：斑马鱼已被广泛用作研究脊椎动物发育和遗传学的模型动物。众所周知，斑马鱼基因的遗传学研究可以深入了解保守的脊椎动物基因的功能，从而更好地了解人类疾病和健康。随着斑马鱼基因组测序项目接近完成，非常希望通过测序预测的所有基因也都携带易于用于基因功能研究的突变。为了实现这一目标，我们开发了一个高效且简化的平台，使用原病毒插入结合高通量测序和作图技术来诱变斑马鱼基因组中基本上所有可识别的候选基因。在这个项目中，我们建议通过构建斑马鱼品系库向公共研究界提供遗传工具，其中大约 12,000 个斑马鱼基因已通过逆转录病毒插入而被破坏。生成的所有资源将在发布前以最低成本提供给社区。公共健康相关性：斑马鱼是研究发育和人类疾病的流行脊椎动物模型生物，我们使用最先进的技术在大多数斑马鱼基因中产生突变。由于这些基因高度保守，我们的研究将为了解人类疾病和协助设计新的治疗方法提供有价值的信息。