I am currently working in the Murry Lab with the KOMP Embyro Phenotyping Project. The Knockout Mouse Project (KOMP) is a trans-National Institutes of Health (NIH) initiative that aims to generate a comprehensive and public resource comprised of mice containing a null mutation in every gene in the mouse genome. At least one third of all homozygous knockouts are expected to be embryonic lethal. My work with the KOMP project is to characterize these mouse models that are homozygous embryonic lethal and document phenotypes and at which point they become lethal. I capture basic information for more extensive subsequent analysis. All of the data that is collected is made public by the central Data Coordination Center Database.
Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.