Sumo-1 Function Is Dispensable in Normal Mouse Development

Abstract

To elucidate SUMO-1 functions in vivo, we targeted by homologous recombination the last three exons of the murine Sumo-1 gene. Sumo-1 mRNA abundance was reduced to one-half in heterozygotes and was undetectable in Sumo-1^−/− mice, and SUMO-1-conjugated RanGAP1 was detectable in wild-type mouse embryo fibroblasts (MEFs) but not in Sumo-1^−/− MEFs, indicating that gene targeting yielded Sumo-1-null mice. Sumo-1 mRNA is expressed in all tissues of wild-type mice, and its abundance is highest in the testis, brain, lungs, and spleen. Sumo-2 and Sumo-3 mRNAs are also expressed in all tissues, but their abundance was not upregulated in Sumo-1-null mice. The development and function of testis are normal in the absence of Sumo-1, and Sumo-1^−/− mice of both sexes are viable and fertile. In contrast to a previous report (F. S. Alkuraya et al., Science 313:1751, 2006), we did not observe embryonic or early postnatal demise of Sumo-1-targeted mice; genotypes of embryos and 21-day-old mice were of predicted Mendelian ratios, and there was no defect in lip and palate development in Sumo-1^+/− or Sumo-1^−/− embryos. The ability of Sumo-1^−/− MEFs to differentiate into adipocyte was not different from that of wild-type MEFs. Collectively, our results support the notion that most, if not all, SUMO-1 functions are compensated for in vivo by SUMO-2 and SUMO-3.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

We thank Saija Kotola, Johanna Iso-Oja, and Katja Kiviniemi for excellent technical assistance; the personnel of the animal facility for taking care of the mice; and Katja Helenius for advice in adipocyte differentiation experiments. We are grateful to the German Mouse Clinic (GSF National Research Center for Environment and Health, Neuherberg, Germany) for phenotype screening of Sumo-1-targeted mice.

This study was supported by grants from the Academy of Finland, Biocentrum Helsinki, the Sigrid Jusélius Foundation, the Finnish Foundation for Cancer Research, the Paulo Foundation, the Oskar öflund Foundation, the Finnish Medical Foundation, Helsinki University Central Hospital, the Research and Science Foundation of Farmos, and the European Union (contract no. LSHM-CT-2005-018652).