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（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，斑马鱼基因的遗传研究可以提供对保守脊椎动物基因功能的见解，因此可以更好地了解人类疾病和健康。随着斑马鱼基因组测序项目几乎完成了，高度希望通过测序依靠的所有基因也将带有一个容易用于基因功能研究的突变。为了实现这一目标，我们使用前病毒插入以及高通量测序和映射技术开发了一个高效且流线的平台，以诱变斑马鱼基因组中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菌株图书馆为公共研究界提供遗传工具，其中大约12,000个斑马鱼基因被逆转录病毒插入中断了。在发布之前，生成的所有资源将以最低的成本提供给社区。公共卫生相关性：斑马鱼是一种流行的脊椎动物模型生物体，用于研究发展和人类疾病，我们使用艺术技术来在大多数斑马鱼基因中产生突变。由于这些基因是高度保守的，我们的研究将提供有价值的信息，以理解人类疾病并协助新型治疗方法设计。