Consortium for Broad Based Disease Phenotyping of Knockout Mice

描述(由申请人提供)：所有基因的全面功能注释是未来哺乳动物系统和生物医学科学研究的关键目标。我们已经建立了一个小鼠突变的大规模表型研究联盟，这是研究基因功能的基础。Bash财团、德克萨斯州休斯敦的贝勒医学院(BCM)、英国Hinxton的Wellcome Trust Sanger研究所老鼠遗传学计划以及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，目的是确定发育、生理和生化途径的扰动，指导实验人员将假设驱动的研究发展到疾病系统中。我们的目标是1)完成C57BL/6N遗传背景下1500多个突变小鼠品系的广泛疾病表型鉴定，2)验证优化和增强的广基表型鉴定管道，该管道将检测各种疾病表型并提高吞吐量，3)向指定的数据协调中心提交表型数据，确保与更广泛的生物医学科学界的接口，为人类遗传学研究提供信息。我们的方法是以我们在小鼠表型鉴定方面的独特专业知识和EUCOMM和KOMP突变体小鼠表型鉴定主要试点项目的成功运作为基础，提供具有战略广度的表型鉴定管道，以满足医学界的需求。我们的流水线设计旨在提供关键治疗相关领域的小鼠模型-例如心血管、新陈代谢、神经、呼吸系统和免疫系统。使用我们的表型流程对小鼠突变进行评估将发现具有治疗重要性的新的临床前模型，包括许多在整个发达国家占疾病发病率最高的疾病。 相关性：一个人的大多数基因都是正常的，但我们也携带着数百个断裂的基因。虽然一些断裂的基因会导致严重的疾病，如囊性纤维化或癌症，但另一些基因几乎没有什么后果，或者只有在压力下才能发挥作用。目前，我们只对三分之一的人类基因的功能有了一些了解。如果我们要充分了解人类的健康和疾病，我们必须利用小鼠等模式生物，将基因功能的知识扩展到我们所有的基因。

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.