Streamline assessment of early lethal phenotypes in the mouse

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， 哺乳动物基因组建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。

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.