Streamline assessment of early lethal phenotypes in the mouse

对小鼠早期致死表型的简化评估。 尽管在小鼠基因组的每个座位上产生功能缺失等位基因的工作正在顺利进行中， 是已建立的评估早期致死表型的管道中的一个缺口(如PAR-17-005所述)。在这里我们 建议继续我们的努力，以确定受精之间发生的多达150个早期致死表型 和器官发生。如中所述，我们已经制定了一种有效的策略来分析早期致死 并已经分析了100多种新的表型。我们将提供巨额资金 将新数据提供给科学界，并促进合作努力，以实现对 哺乳动物的基因组。这项拟议的工作充分利用了我们小组执行和发布的技术 通常，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，进行个人研究计划。基因敲除等位基因的特征将 对于了解遗传途径和疾病/表型的预测机制是非常宝贵的 在成人中发现-在基因/蛋白质网络中的杂合子和纯合子基因敲除中或 小路。我们将为每个突变表型提供详细的形态发生特征。 新的原肠胚和着床前表型的特征将补充和扩展我们目前的 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工作完全吻合，并满足了早期表征的基本需要 致命性表型对基因组的功能注释。

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.