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：
8333401
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/8333401
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对哺乳动物系统和生物医学科学的未来研究的关键目标。我们已经建立了一个用于小鼠突变体大规模表型的联盟，这是基因功能研究的基础。 BASH联盟，贝勒医学院（BCM），德克萨斯州休斯敦，惠康信托基金会桑格研究所鼠标遗传学计划，欣克斯顿，英国，英国和医学研究委员会Harwell（英国哺乳动物遗传学单位和玛丽·里昂中心），英国，将对300 IKMC鼠标的基于较广泛的表型分析，并将对300 IKMC鼠标的广泛分析进行，并将生化途径将指导实验者开发以假设为导向疾病系统的研究。 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.我们的方法是基于我们在鼠标表型中的独特专业知识以及主要试点项目的成功运作，用于鼠标和科普突变体的鼠标表型，以提供具有策略广度的表型管道，以满足医疗社区需求。我们的管道设计旨在在关键的治疗领域提供小鼠模型，例如在心血管，代谢，神经系统，呼吸系统和免疫系统中。使用我们的表型管道对小鼠突变体进行评估将发现治疗重要性的新型临床前模型，其中包括许多疾病，这些疾病是整个发达国家疾病发病率最高的疾病。相关性：一个人中的大多数基因都是正常的，但我们也携带了数百个基因。尽管某些破裂的基因会引起严重的疾病，例如囊性纤维化或癌症，但其他基因几乎没有任何后果，或者仅在压力下起作用。目前，我们对仅三分之一的人类基因的功能有所了解。如果我们要充分了解人类健康和疾病，则必须使用小鼠等模型生物扩大对所有基因的知识。