Homozygotes for a targeted null mutation accumulate cyclin E, exhibit abnormal cycling in cells of extraembryonic ectoderm and trophectoderm, reduced size, abnormal gastrulation and trophoblast cells, absence of an amnion, and death by embryonic day 7.5. Conditional heterozygous KO in neuronal cells causes social deficits and anxiety-like behavior, while homozygous neuronal KO leads to brain abnormalities, small body size and death before weaning.