Sumo-1 Function Is Dispensable in Normal Mouse Development

To elucidate SUMO-1 functions in vivo, we targeted by homologous recombination the last three exons of the murineSumo-1 gene.Sumo-1 mRNA abundance was reduced to one-half in heterozygotes and was undetectable inSumo-1 −/− mice, and SUMO-1-conjugated RanGAP1 was detectable in wild-type mouse embryo fibroblasts (MEFs) but not inSumo-1 −/− MEFs, indicating that gene targeting yieldedSumo-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 andSumo-3 mRNAs are also expressed in all tissues, but their abundance was not upregulated inSumo-1 -null mice. The development and function of testis are normal in the absence ofSumo-1 , andSumo-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 ofSumo-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 inSumo-1 +/− orSumo-1 −/− embryos. The ability ofSumo-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.