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Streamline assessment of early lethal phenotypes in the mouse

简化小鼠早期致死表型的评估

基本信息

批准号：
9257443
负责人：
Jesse Mager
金额：
$ 66.48万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-15 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9257443
关键词：
Address Adult Alleles Behavioral Breeding Cardiovascular system Categories Cells Classification Communities Congenital Abnormality Data Databases Defect Development Disease Embryo Embryonic Development Ensure Event Fertilization Fostering Gene Targeting Generations Genes Genetic Goals Individual Informatics International Investments Knock-out Knockout Mice Link Morphology Mus Nature Organ Organogenesis Pathway interactions Phenotype Physiological Production Productivity Publishing Recovery Regenerative Medicine Research Resources Standardization Techniques Time Tissues Training Work blastocyst early embryonic stage experience gastrulation gene function genome annotation implantation in vitro Assay in vivo interest knowledge base loss of function mammalian genome mouse genome mutant novel phenotypic data preimplantation programs public health relevance stem cell biology success zygote

项目摘要

DESCRIPTION (provided by applicant): Streamline assessment of early lethal phenotypes in the mouse. Although the generation of a loss of function allele at every locus in the mouse genome is well underway, there is a gap in established pipelines for assessment of early lethal phenotypes. Here we propose a simple and efficient strategy for characterization of up to 200 early lethal phenotypes occurring between fertilization and organogenesis. The proposed work capitalizes on techniques that our team performs and publishes routinely, maximizing the data generation by eliminating training and troubleshooting steps as well as boosting our individual research programs by providing novel phenotypes of interest. Our strategy relies on an initial morphological assessment of mutant phenotypes and classification into three different categories: pre- implantation, gastrulation and post-gastrulation lethals. A second round of analysis will provide a more detailed analysis of the phenotype. The characterization of early embryonic lethal alleles will be invaluable towards understanding genetic pathways of basic embryo development providing new directions for studies in stem cell biology and regenerative medicine. Our proposal dovetails perfectly with existing phenotyping efforts and fills an essential need to characterize early lethal phenotypes towards functional annotation of the genome.

描述（由申请方提供）：小鼠早期致死表型的简化评估。虽然在小鼠基因组中的每个位点上产生功能丧失等位基因的工作正在顺利进行，但在评估早期致死表型的既定管道中存在空白。在这里，我们提出了一个简单而有效的策略，多达200个早期致命的受精和器官发生之间发生的表型的特征。拟议的工作利用了我们团队定期执行和发布的技术，通过消除培训和故障排除步骤来最大限度地生成数据，并通过提供感兴趣的新表型来促进我们的个人研究计划。我们的策略依赖于突变表型的初始形态学评估和分为三个不同类别的分类：着床前、原肠胚形成和原肠胚形成后致死。第二轮分析将提供更详细的表型分析。早期胚胎致死等位基因的特征将是非常宝贵的了解基本胚胎发育的遗传途径，为干细胞生物学和再生医学的研究提供新的方向。我们的建议与现有的表型分析工作完美吻合，需要表征基因组功能注释的早期致死表型。