Onset of embryonic and placental defects coincide in 19 of 22 novel mid-gestation lethal murine knockout lines

The focus on assessing embryo-specific defects in lethal knockout (KO) mouse lines has resulted in an underrepresentation of documented placental abnormalities. Presented herein is a uniform analysis of 22 distinct KO mouse lines that exhibit homozygous lethality in a narrow mid-gestation window. All genes altered by each KO have human orthologs, most are implicated in human disease, yet almost all are understudied. To unravel the role each plays in mammalian development, null embryonic and placental phenotype analysis was performed, and wild type (WT) expression of each KO gene was assessed. While the null phenotype of each KO line falls into two broad embryonic categories, the placental phenotypes are diverse and coincide with the onset of gross embryonic defects. The co-occurrence of null embryonic and placental defect onset coupled with WT gene expression highlights that many could be essential in either the embryo or placenta. This analysis serves to guide mid-gestation placental analysis, underscores the importance of routine analysis of the entire conceptus during mid-gestation lethality, and provides functional annotation for each understudied human ortholog.