The period of development between the zygote and embryonic day 9.5 in mice includes multiple developmental milestones essential for embryogenesis. The preeminence of this period of development has been illustrated in loss of function studies conducted by the International Mouse Phenotyping Consortium (IMPC) which have shown that close to one third of all mouse genes are essential for survival to weaning age and a significant number of mutations cause embryo lethality before E9.5. Here we report a systematic analysis of 21 pre-E9.5 lethal lines generated by the IMPC. Analysis of pre- and post-implantation embryos revealed that the majority of the lines exhibit mutant phenotypes that fall within a window of development between implantation and gastrulation with few pre-implantation and no post-gastrulation phenotypes. Our study provides multiple genetic inroads into the molecular mechanisms that control early mammalian development and the etiology of human disease, in particular, the genetic bases of infertility and pregnancy loss. We propose a strategy for an efficient assessment of early embryonic lethal mutations that can be used to assign phenotypes to developmental milestones and outline the time of lethality
