A DNMT3B (DNMT3B , DNA (cytos ine-5)methyltransferase 3B; Swiss-Prot accession number: Q9UBC3) gene deletion construct in which exons 16–19 were deleted was used to generate Dnmt3b-null ES cells and animals. The deleted region encodes the highly conserved PC (proline cysteine) and ENV (glutamic acid, asparagine, valine) motifs that are crucial for catalytic activity [1,2]. Targeted replacement of the wild -type sequence with this deleted construct renders the protein catalytically inactive. Dnmt3b-/knockout mice show embryonic lethality between embryonic day (E) 13.5 and E16.5. Embryos at that stage show subcutaneous edema and liver atrophy, with some embryos showing ectopic hemorrhage of the head region. In addition, serial sections of Dnmt3b-null mice at E14.5 and E15.5 revealed that the ventricular septum of the heart was not closed. Although these mice do not directly model any known human disease, they are crucial in demonstrating the importance of DNMT3B in early development and organogenesis [2].