SUMO 2 is essential while SUMO 3 is dispensable for mouse embryonic development

Small ubiquitin‐like modifier ( SUMO 1–3) conjugation plays a critical role in embryogenesis. Embryos deficient in the SUMO ‐conjugating enzyme Ubc9 die at the early postimplantation stage. Sumo1 −/− mice are viable, as SUMO 2/3 can compensate for most SUMO 1 functions. To uncover the role of SUMO 2/3 in embryogenesis, we generated Sumo2‐ and Sumo3‐ null mutant mice. Here, we report that Sumo3 −/− mice were viable, while Sumo2 −/− embryos exhibited severe developmental delay and died at approximately embryonic day 10.5 (E10.5). We also provide evidence that SUMO 2 is the predominantly expressed SUMO isoform. Furthermore, although Sumo2 +/− and Sumo2 +/− ;Sumo3 +/− mice lacked any overt phenotype, only 2 Sumo2 +/− ;Sumo3 −/− mice were found at birth in 35 litters after crossing Sumo2 +/− ;Sumo3 +/− with Sumo3 −/− mice, and these rare mice were considerably smaller than littermates of the other genotypes. Thus, our findings suggest that expression levels and not functional differences between SUMO 2 and SUMO 3 are critical for normal embryogenesis.