Streamline assessment of early lethal phenotypes in the mouse

Although generation of loss of function alleles at every locus in the mouse genome is underway, there is a gap in established pipelines for assessment of early lethal phenotypes (as stated in PAR-23-074). Here we continue our efforts and characterize an additional 10-15 early lethal phenotypes occurring between fertilization and organogenesis. As described within, we have instituted an efficient strategy and have already analyzed more than 250 alleles. 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 group performs routinely, maximizing the data generation by eliminating training/troubleshooting steps as well as in depth analysis of select phenotypes of interest. Phenotyping of knock-out alleles is invaluable towards understanding genetic pathways and predicting mechanisms of adult diseases/phenotypes. Characterization of newly generated alleles with gastrulation and preimplantation phenotypes will complement and extend our current morphogenetic understanding of early developmental events. Our proposal dovetails perfectly with existing KOMP/IMPC efforts and fills an essential need to characterize early lethal phenotypes towards functional annotation of the genome.