High-throughput discovery of novel developmental phenotypesMore about Open Access at the Crick
Authors listMary E Dickinson Ann M Flenniken Xiao Ji Lydia Teboul Michael D Wong Jacqueline K White Terrence F Meehan Wolfgang J Weninger Henrik Westerberg Hibret Adissu Candice N Baker Lynette Bower James M Brown L Brianna Caddle Francesco Chiani Dave Clary James Cleak Mark J Daly James M Denegre Brendan Doe Mary E Dolan Sarah M Edie Helmut Fuchs Valerie Gailus-Durner Antonella Galli Alessia Gambadoro Juan Gallegos Shiying Guo Neil R Horner Chih-Wei Hsu Sara J Johnson Sowmya Kalaga Lance C Keith Louise Lanoue Thomas N Lawson Monkol Lek Manuel Mark Susan Marschall Jeremy Mason Melissa L McElwee Susan Newbigging Lauryl MJ Nutter Kevin A Peterson Ramiro Ramirez-Solis Douglas J Rowland Edward Ryder Kaitlin E Samocha John R Seavitt Mohammed Selloum Zsombor Szoke-Kovacs Masaru Tamura Amanda G Trainor Ilinca Tudose Shigeharu Wakana Jonathan Warren Olivia Wendling David B West Leeyean Wong Atsushi Yoshiki The International Mouse Phenotyping Consortium Daniel G MacArthur Glauco P Tocchini-Valentini Xiang Gao Paul Flicek Allan Bradley William C Skarnes Monica J Justice Helen E Parkinson Mark Moore Sara Wells Robert E Braun Karen L Svenson Martin Hrabe de Angelis Yann Herault Tim Mohun Ann-Marie Mallon R Mark Henkelman Steve DM Brown David J Adams KC Kent Lloyd Colin McKerlie Arthur L Beaudet Maja Bućan Stephen A Murray
Toggle all authors (84)
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.