SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development

Small ubiquitin-like modifier (SUMO1-3) 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 SUMO2/3 can compensate for most SUMO1 functions. To uncover the role of SUMO2/3 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 SUMO2 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 SUMO2 and SUMO3 are critical for normal embryogenesis.