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Open Access

SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development

Liangli Wang, Carolien Wansleeben, Shengli Zhao, Pei Miao, Wulf Paschen, Wei Yang

Author Affiliations

  1. Liangli Wang1,
  2. Carolien Wansleeben2,
  3. Shengli Zhao3,
  4. Pei Miao1,
  5. Wulf Paschen*,1 and
  6. Wei Yang*,1
  1. 1Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA
  2. 2Department of Cell Biology, Duke University Medical Center, Durham, NC, USA
  3. 3Department of Neurobiology, Duke University Medical Center, Durham, NC, USA
  1. * Corresponding author. Tel: +1 919 684 5576; Fax: +1 919 684 6692; E‐mail: wulf.paschen{at}duke.edu

    Corresponding author. Tel: +1 919 684 6573; Fax: +1 919 684 6692; E‐mail: wei.yang{at}duke.edu

Abstract

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.

Synopsis

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This study shows that SUMO2 loss is embryonic lethal while Sumo3−/− mutants lack an overt phenotype, although both isoforms are highly homologous. The data suggest that expression levels and not functional differences between SUMO2 and SUMO3 are critical for embryonic development.

  • Sumo3−/− mice are viable

  • Sumo2−/− embryos die at approximately embryonic day 10.5

  • SUMO2 is the predominantly expressed SUMO isoform

  • Received January 22, 2014.
  • Revision received April 3, 2014.
  • Accepted April 22, 2014.

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