CUL-4A Is Critical for Early Embryonic Development

• DOI: 10.1128/mcb.22.14.4997-5005.2002
• Publication Date: 2002-07-28T23:07:23Z
• Authors: Binghui Li; Joseph C. Ruiz; Kristin T. Chun
• Keywords: Haploinsufficiency

Ubiquitin-mediated degradation targets cell cycle regulators for proteolysis.Much of the ubiquitin pathway's substrate specificity is conferred by E3 ligases, and cullins are core components some E3s.CUL-4A encodes one six mammalian amplified and/or overexpressed in breast cancer, which suggests a role regulating progression.To examine CUL-4A's physiologic function, we generated CUL-4A deletion mutation mice.No viable ؊/؊ pups no homozygous mutant embryos as early 7.5 days postcoitum (dpc) were recovered.However, blastocysts viable, hatch, form an inner mass trophectoderm, implant (roughly 4.5 dpc), indicating that die between dpc.Despite 87% similarity Cul-4A Cul-4B cullins, lethal phenotype indicates has or more distinct function(s).Surprisingly, 44% fewer heterozygous recovered than expected Mendelian genetics, many also during gestation due to haploinsufficiency.Taken together, our findings indicate appropriate expression critical embryonic development.