Up to one third of homozygous knockout lines are lethal, which means no homozygous mice or less than expected are observed past the weaning stage (IMPC Viability Primary Screen procedure). Early death may occur during embryonic development or soon after birth, during the pre-weaning stage. For this reason, the IMPC established a systematic phenotyping pipeline to morphologically evaluate mutant embryos to ascertain the primary perturbations that cause early death and thus gain insight into gene function.
As determined in IMPReSS (see interactive diagram here), all embryonic lethal lines undergo gross morphology assessment at E12.5 (embryonic day 12.5) to determine whether defects occur earlier or later duirng embryonic development. A comprehensive imaging platform is then used to assess dysmorphology. Embryo gross morphology, as well as 2D and 3D imaging are actively being implemented by the IMPC for lethal lines.
Read more in our paper on High-throughput discovery of novel developmental phenotypes, Nature 2016