Mice lacking DCAF2 in placenta die at the gastrulation stage.

UV-damaged DNA-binding protein 1 (DDB1) and cullin 4-associated factor 2 (DCAF2, also known as DTL or CDT2) is an evolutionarily highly conserved substrate recognition factor in the cullin 4 RING E3 ubiquitin ligase (CRL4) complex. This complex degrades multiple DNA replication and cell cycle-associated proteins to maintain genome stability. To clarify the function of DCAF2 in vivo, we used Cre recombinase driven by the Elf5 promoter to generate knockout mouse model that was specifically deleted Dcaf2 in the trophoblast lineage (Elf5-Cre; Dcaf2fl/fl, Dcaf2 cKO). Here, we show that mice with the genotype Elf5-Cre; Dcaf2fl/+ are normal and fertile. However, after mating of Elf5-Cre; Dcaf2fl/+ mice with Dcaf2fl/fl, no Dcaf2 cKO pups were born. Timed pregnancy studies have shown that Dcaf2 cKO mice developed abnormally on embryonic day 5.5 and died at gastrulation stage. It is worth noting that the extraembryonic ectoderm of Dcaf2 cKO mice is severely reduced or missing and leading to embryonic death. We also proved that stronger DNA damage accumulated in the trophoblastic cells of Dcaf2 cKO mice at E8.5. In addition, higher expression of Caspase-3 was found in the embryonic and trophoblastic cells of these cKO mice. In general, our research shows that the placental DCAF2 is crucial to the formation of gastrula.