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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：
10256081
负责人：
Jesse Mager
金额：
$ 63.11万
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：
2015-09-08 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10256081
关键词：
Address Adult Alleles Award Back Categories Cell Lineage Cells Charge Communities Complement Congenital Abnormality Data Databases Defect Development Disease Embryo Embryonic Development Endoderm Ensure Epiblast Event Failure Fertilization First Independent Research Support and Transition Awards Fostering Gene Proteins Generations Genes Genetic Goals Heterozygote Individual Institutes International Investments Knock-out Knockout Mice Link Morphology Mus Nature Organ Organogenesis Pathway interactions Phenotype Production Productivity Publishing Recovery Regenerative Medicine Research Resources Standardization Techniques Training United States National Institutes of Health Work base blastocyst cohort disease phenotype early embryonic stage experience failure Implantation gastrulation gene function genome annotation human disease interest knock out mouse project knockout gene knowledge base loss of function mammalian genome mouse genome mutant novel phenotypic data preimplantation progenitor programs stem cell biology success zygote

项目摘要

PROJECT SUMMARY 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 (as stated in PAR-17-005). Here we propose to continue our efforts to characterize up to 150 early lethal phenotypes occurring between fertilization and organogenesis. As described within, we have instituted an efficient strategy to analyze early lethal phenotypes and have already analyzed more than 100 novel phenotypes. We will provide a tremendous amount of novel data to the scientific community and foster collaborative efforts towards functional annotation of the mammalian genome. The proposed work capitalizes on techniques that our groups perform and publish routinely, maximizing the data generation by eliminating training/troubleshooting steps as well as boosting our individual research programs by providing novel phenotypes of interest. Characterization of knock-out alleles will be invaluable towards understanding genetic pathways and predicting mechanisms of diseases/phenotypes found in adults – in both heterozygotes and homozygous knockouts of genes in gene/protein networks or pathways. We will provide detailed morphogenetic characterization for each mutant phenotype. Characterization of novel gastrulation and preimplantation phenotypes will complement and extend our current morphogenetic understanding of early developmental events. Our proposal dovetails perfectly with existing phenotyping efforts and fills an essential need to characterize early lethal phenotypes towards functional annotation of the genome.

项目摘要小鼠早期致死表型的简化评估尽管在小鼠基因组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，是评估早期致死表型的既定管道中的一个空白（如PAR-17-005所述）。这里我们我建议继续我们的努力，以确定多达150个早期致命的表型之间发生受精和器官形成。如内所述，我们已经制定了一个有效的战略，以分析早期致命的表型，并已分析了100多个新的表型。我们会提供大量的向科学界提供新数据，并促进合作努力，哺乳动物基因组拟议的工作利用了我们小组执行和发布的技术通过消除培训/故障排除步骤以及提高我们的通过提供新的感兴趣的表型的个人研究计划。敲除等位基因的表征将对理解遗传途径和预测疾病/表型的机制非常宝贵在成人中发现-在基因/蛋白质网络中基因的杂合子和纯合子敲除中，或途径。我们将提供每个突变表型的详细形态发生学特征。新的原肠胚形成和植入前表型的表征将补充和扩展我们目前的研究。对早期发育事件的形态发生学理解。我们的建议与现有的表型分析工作完美吻合，并满足了早期表征的基本需求。致死表型对基因组的功能注释。