Consortium for Broad Based Disease Phenotyping of Knockout Mice

基因敲除小鼠广泛疾病表型联盟

基本信息

批准号：
8189488
负责人：
MONICA J. JUSTICE
金额：
$ 264.2万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-16 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8189488
关键词：
Accounting Animal Model Area Biochemical Pathway Biological Assay Cardiovascular system Communities Cystic Fibrosis Data Data Coordinating Center Data Quality Data Set Development Disease Ensure Funding Future Genes Genetic Genetic Programming Goals Health Human Human Genetics Inbred Strain Institutes International Investigation Knockout Mice Knowledge Laboratories Learning Malignant Neoplasms Mammalian Genetics Measurement Medical Medical Research Medicine Metabolic Morbidity - disease rate Mus Mutant Strains Mice Neurologic Persons Phenotype Physiological Pilot Projects Pre-Clinical Model Research Research Personnel Resources Science Scientist Sensitivity and Specificity Stress Symptoms System Texas Therapeutic Trust United Kingdom Work base college design disease phenotype embryonic stem cell experience gene function genetic variant high throughput screening improved interest member mouse genome mouse model mutant novel novel strategies operation pleiotropism respiratory tool

项目摘要

DESCRIPTION (provided by applicant): A comprehensive functional annotation of all genes is a key goal for the future investigation of mammalian systems and biomedical sciences. We have established a consortium for the large-scale phenotyping of mouse mutants, which is fundamental to the investigation of gene function. The BaSH consortium, Baylor College of Medicine (BCM), Houston, Texas, the Wellcome Trust Sanger Institute Mouse Genetics Programme, Hinxton, United Kingdom, and the Medical Research Council Harwell, (Mammalian Genetics Unit and Mary Lyon Centre), United Kingdom, will undertake broad-based phenotype analysis of 300 IKMC mouse lines per year with the aim of identifying perturbations on developmental, physiological and biochemical pathways that will guide experimenters to develop hypothesis-driven research into disease systems. Our aims are to 1) complete the broad-based disease phenotyping of over 1500 lines of mutant mice in the C57BL/6N genetic background, 2) validate an optimized and enhanced broad-based phenotyping pipeline that will detect a variety of disease phenotypes and increase throughput, and 3) submit phenotypic data to the designated data coordination center, ensuring an interface with the wider biomedical scientific community that will inform human genetic studies. Our approach is to build on our unique expertise in mouse phenotyping and the successful operation of major pilot projects for mouse phenotyping of EUCOMM and KOMP mutants to deliver a phenotyping pipeline with strategic breadth that serves the needs of the medical community. Our pipeline design aims to deliver mouse models in key therapeutically relevant areas - for example in Cardiovascular, Metabolic, Neurological, Respiratory and Immunological Systems. Assessment of mouse mutants using our phenotyping pipeline will discover novel preclinical models of therapeutic importance, encompassing many of the diseases that account for the highest rates of disease morbidity throughout the developed world. RELEVANCE: Most of the genes in a person are normal, but we also carry several hundred broken ones. While some broken genes can cause severe disease such as cystic fibrosis or cancer, others have little of no consequence, or function only under stress. Currently, we have some understanding of the function of just one third of human genes. If we are to fully understand human health and disease we must expand knowledge of gene function to all of our genes using model organisms such as the mouse.

描述（由申请人提供）：所有基因的全面功能注释是哺乳动物系统和生物医学科学未来研究的关键目标。我们已经建立了一个对小鼠突变体进行大规模表型分析的联盟，这对于基因功能的研究至关重要。 BaSH 联盟、德克萨斯州休斯敦贝勒医学院 (BCM)、英国欣克斯顿威康信托桑格研究所小鼠遗传学项目和英国哈威尔医学研究委员会（哺乳动物遗传学单位和玛丽里昂中心），将每年对 300 个 IKMC 小鼠品系进行广泛的表型分析，目的是识别发育、生理和生化途径的扰动，从而指导实验人员开发假设驱动的疾病系统研究。我们的目标是 1) 完成 C57BL/6N 遗传背景下 1500 多个突变小鼠系的广泛疾病表型分析，2) 验证优化和增强的广泛表型分析管道，该管道将检测多种疾病表型并增加吞吐量，3) 将表型数据提交给指定的数据协调中心，确保与更广泛的生物医学科学界建立联系，为人类遗传学研究提供信息。我们的方法是利用我们在小鼠表型分析方面的独特专业知识以及 EUCOMM 和 KOMP 突变体小鼠表型分析重大试点项目的成功运作，提供具有战略广度的表型分析管道，满足医学界的需求。我们的管道设计旨在提供关键治疗相关领域的小鼠模型 - 例如心血管、代谢、神经、呼吸和免疫系统。使用我们的表型分析流程对小鼠突变体进行评估将发现具有治疗重要性的新型临床前模型，涵盖许多发达国家发病率最高的疾病。相关性：人体内的大多数基因都是正常的，但我们也携带数百个损坏的基因。虽然一些断裂的基因可能导致囊性纤维化或癌症等严重疾病，但其他基因则几乎没有任何后果，或者仅在压力下发挥作用。目前，我们对人类基因的功能只有三分之一有一定的了解。如果我们要充分了解人类健康和疾病，我们必须使用模型生物（例如小鼠）将基因功能的知识扩展到我们所有的基因。