Nature 555, 463–468 (2018).

Creating knock-out mouse lines doesn’t always go as planned—previous phenotyping efforts have suggested that in as many as 25–30% of cases, knock-out offspring just won’t be viable. Researchers studying why have tended to focus on deleterious effects to the growing embryo, but they haven’t paid as much attention to another important consideration for proper development: the placenta.

A recent systematic screen of 103 different knock-out mice pins over half of the problems that arise during gestation on mutations that affect the placenta. As gestation continues, those defects in the placenta appear to be linked to abnormalities in the embryo, especially in the brain, heart, and vasculature. Further testing implicated genes related to the trophoblast, the outer layer of the placenta that provides nutrition to the embryo.