Streamline assessment of early lethal phenotypes in the mouse

 描述(由申请人提供)：简化对小鼠早期致死表型的评估。尽管小鼠基因组中每个基因座功能缺失等位基因的产生正在顺利进行，但在评估早期致死表型方面，已建立的管道存在缺口。在这里，我们提出了一种简单而有效的策略来描述发生在受精和器官发生之间的多达200个早期致命表型。拟议的工作利用了我们团队常规执行和发布的技术，通过消除培训和故障排除步骤来最大化数据生成，以及通过提供感兴趣的新表型来促进我们的个人研究计划。我们的策略依赖于对突变表型的初步形态评估，并将其分为三个不同的类别：植入前、原肠形成和原肠形成后死亡。第二轮分析将提供对表型的更详细分析。早期胚胎致死等位基因的特征对于了解基本胚胎发育的遗传途径将是非常有价值的，为干细胞生物学和再生医学的研究提供了新的方向。我们的建议与现有的表型鉴定工作完美吻合，并填补了必要的 需要表征基因组功能注释的早期致死表型。

 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.