Embryonic lethality in mice lacking CUL1, CUL3, or CUL4a occurs at the early stage of embryo formation (E4.5-E7.5) before organ formation, while mice lacking CUL7 show neonatal lethality and severe intrauterine growth retardation (IUGR) with significantly smaller foetuses and placental anomalies, indicating that the mechanisms by which CUL7 and the other three CUL E3 ligases mediate mammalian development are obviously distinct. This evidence concerns the gene CUL4A and fetal growth restriction.