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 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.
Zhang
Fu-Ping
FP
University of Helsinki, Institute of Biomedicine (Physiology), Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), FI-00014 Helsinki, Finland.
Mikkonen
Laura
L
Toppari
Jorma
J
Palvimo
Jorma J
JJ
Thesleff
Irma
I
Jänne
Olli A
OA
D050156:Adipogenesis; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010159:Palate / Q000166:cytology / Q000196:embryology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000196:embryology; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D025842:SUMO-1 Protein; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; C117908:Sumo3 protein, mouse; D014452:Ubiquitins