Streamline assessment of early lethal phenotypes in the mouse

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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.