Gene targeted rat resource for the study of complex disease

用于复杂疾病研究的基因靶向大鼠资源

• 批准号: 8729003
• 负责人: HOWARD J JACOB
• 金额: $ 184.4万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8729003
• 关键词: Animal Model; Animals; Cells; Collection; Communities; Complex; Cryopreservation; Data; Development; Disasters; Disease; Ensure; Fibroblasts; Funding; Gene Targeting; Gene-Modified; Genes; Genetic; Genomics; Grant; Health; Human; Human Resources; Investments; Lead; Letters; Modeling; Monoclonal Antibody R24; Persons; Phenotype; Physiological; Physiology; Principal Investigator; Process; Quantitative Trait Loci; Rat Strains; Rattus; Reagent; Recovery; Research Infrastructure; Research Personnel; Resource Development; Resources; Risk; Rodent; Savings; Science; Services; System; Technology; Testing; Tissue Banking; Tissue Banks; Tissues; United States National Institutes of Health; Zinc Fingers; abstracting; cost; cost effective; embryonic stem cell; experience; follow-up; genome wide association study; interest; meetings; member; novel; nuclease; operation; programs; skills; sperm cell; tool; trait

DESCRIPTION (provided by applicant): Using the zinc finger nucleases (ZFN) technology for making gene modification or edits we generated 101 strains within two years. The ZFN technology is extraordinarily efficient and does not require the use of embryonic stem cells, as a result any rat strain should be able to be rapidly (3 to 6 months) modified. This R24 resource grant enables our existing infrastructure: personnel, expertise in gene editing, high throughput phenotyping, distribution channels resulting in an economies of scale that can be leverage to generate novel and important rat models to more investigators. The unique rat models already developed by our existing program, have demonstrated: 1) that the infrastructure is already in place to meet our objectives; 2) these gene modified strains can be used to validate a gene underlying a quantitative trait locus, testing a GWAS result, follow-up studies to define function of a predicted gene, or developing a model to study the physiology/mechanisms of a gene; 3) our economy of scale; 4) a full distribution system in place; and 5) over a decade of resources development (data, rats, genetic and genomic reagents) for the rat. To assure the resource meets community needs, we will establish an External Advisory Board (EAB) that will assess our progress, and conduct a scientific merit review process to select the genes and use of the resources of the R24 nominated by the scientific community (Aim 1). We plan to generate 250 gene targeted rat models (Aim 2), to provide a menu of phenotypic characterization that are available, but not required (Aim 3), and cryopreserved sperm from each line, along with a tissue and fibroblast primary culture bank for each strain, as well as distribute all the animals and reagents to the community (Aim 4). Specific aims 1-4 are expected to generate a cost effective and powerful collection of rat models for the community that will accelerate discovery and increase the field's understanding ofthe mechanisms involved in complex diseases. The scientific community has already nominated more than 343 genes demonstrating that the resources developed in this R24 will be of significant value to many investigators. The EAB will assure transparency and that this resource serves the community. (End of Abstract)

描述（由申请人提供）： 使用锌指核酸酶（ZFN）技术进行基因修饰或编辑，我们在两年内产生了101个菌株。 ZFN技术非常有效，不需要使用胚胎干细胞，因此，任何大鼠菌株都应该能够迅速（3至6个月）进行修改。 R24资源授予使我们现有的基础架构：人员，基因编辑专业知识，高 吞吐量表型，分配通道导致规模经济，可以将其作为为更多研究者生成新颖和重要的大鼠模型的杠杆作用。我们现有程序已经开发的独特老鼠模型已经证明：1）已经建立了基础架构来实现我们的目标； 2）这些基因修饰菌株可用于验证定量性状基因座的基因，测试GWAS结果，后续研究以定义预测基因的功能，或开发一个模型来研究基因的生理/机制； 3）规模经济； 4）完整的分配系统； 5）在十年的资源开发（数据，大鼠，遗传和基因组试剂）中，大鼠。为了确保资源满足社区需求，我们将建立一个外部顾问委员会（EAB），该委员会将评估我们的进度，并进行科学功绩审查过程，以选择科学界提名的R24资源的基因和使用（AIM 1）。我们计划生成250个基因靶向大鼠模型（AIM 2），以提供可用但不需要的表型表征菜单（AIM 3），以及每条线的冷冻保存精子，以及每种菌株的组织和成纤维细胞初级培养库，以及将所有动物和经济性分配给社区（AIM 4）。 具体目标1-4有望为大鼠模型产生成本效益和强大的鼠标收集 社区将加速发现并增加该领域对复杂疾病涉及的机制的理解。该科学界已经提名了343多个基因，证明该R24中开发的资源对许多研究人员具有重要价值。 EAB将确保透明度，并且该资源为社区服务。 （抽象的结尾）