Xenopus Mutant Resource

非洲爪蟾突变体资源

• 批准号: 10435421
• 负责人: Marko E Horb
• 金额: $ 75.8万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10435421
• 关键词: Amphibia; Anatomy; Animals; Avidin; Biological Models; Biomedical Research; Biotin; Cellular biology; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; DNA; Data; Destinations; Development; Developmental Biology; Diploidy; Disease; Embryo; Emerging Technologies; Generations; Genes; Genetic; Genetic Models; Goals; Grant; Heritability; Human; Individual; Infrastructure; Injections; Investments; Knock-out; Label; Methods; Modeling; Neurobiology; Oocytes; Organogenesis; Paper; Pathway interactions; Physiology; Proteins; Research; Research Personnel; Resources; Scientist; Signal Transduction; System; Testing; Time; Tissues; Toes; Training; Transgenic Organisms; United States National Institutes of Health; Variant; Veins; Vitellogenins; Work; Xenopus; Xenopus laevis; biomedical resource; experimental study; genome editing; human disease; human model; insight; meetings; molecular mechanics; mutant; new technology; repaired; response; site-specific integration; uptake; water quality; xenopus genome

Project Summary This grant supports a project to generate and characterize Xenopus mutants in key genes related to human disease, establish a new Xenopus Mutant Resource, develop new transgenic lines for genome editing and establish efficient site-specific integration. The long-term goals of the studies are to generate new models of human disease that will provide useful resources for the biomedical research community. The proposed studies will use CRISPR-Cas gene editing to create precise models of human disease in the amphibian Xenopus. The current studies are focused on developing Xenopus models of many different diseases for the entire Xenopus community, and each mutant will be developed in close coordination with individual researchers. There are four main aims to this proposal. First, we propose to collaborate with Xenopus researchers to characterize existing mutants (over 116) that were developed over the last four years. The mutants cover a wide range of topics that require varied expertise that can only be obtained through interactions with other researchers. Second, we propose to generate new mutants using CRISPR-Cas as requested by researchers. As the national stock center for Xenopus, we have the proven expertise to breed and maintain these mutants. Third, we will generate new transgenic lines that will be used for genome editing. These new lines will allow for more tissue-specific expression of Cas9. Fourth, we propose to develop homology directed repair for more efficient generation of site-specific integration of exogenous DNA. All of these aims will help enhance the utilization of CRISPR-Cas gene editing methods in the Xenopus model system.

项目摘要 这笔赠款支持了一个项目，即在与人类相关的关键基因中产生并鉴定非洲爪哇突变株。 疾病，建立新的非洲爪哇突变资源，开发新的转基因系用于基因组编辑和 建立高效的特定地点集成。这些研究的长期目标是产生新的模型 人类疾病，将为生物医学研究界提供有用的资源。建议数 研究将使用CRISPR-Cas基因编辑在两栖动物中创建精确的人类疾病模型 非洲爪哇。目前的研究集中在为非洲爪哇建立许多不同疾病的模型。 整个非洲爪哇群落，每个突变体都将与个体密切协调发展 研究人员。这项提议有四个主要目标。首先，我们建议与Xenopus合作 研究人员对过去四年开发的现有突变体(超过116个)进行了表征。这个 变种人涉及广泛的主题，需要不同的专业知识，而这些专业知识只能通过 与其他研究人员的互动。其次，我们提出使用CRISPR-CAS产生新的突变体 应研究人员的要求。作为非洲爪哇的国家储备中心，我们拥有成熟的养殖技术 并维持这些变种人。第三，我们将产生新的转基因品系，用于基因组编辑。 这些新的品系将允许更多的组织特异性表达Cas9。第四，我们建议发展 同源定向修复更有效地产生外源DNA的位点特异性整合。所有的 这些目标将有助于加强CRISPR-Cas基因编辑方法在非洲爪哇模式中的利用 系统。