Abstract
BackgroundA plethora of biological metabolisms are regulated by the mechanisms of ubiquitination, wherein this process is balanced with the action of deubiquitination system. Dub-2 is an IL-2-inducible, immediate-early gene that encodes a deubiquitinating enzyme with growth regulatory activity. DUB-2 presumably removes ubiquitin from ubiquitin-conjugated target proteins regulating ubiquitin-mediated proteolysis, but its specific target proteins are unknown yet.Methodology/Principal FindingsTo elucidate the functional role of Dub-2, we generated genetically modified mice by introducing neo cassette into the second exon of Dub-2 and then homologous recombination was done to completely abrogate the activity of DUB-2 proteins. We generated Dub-2+/− heterozygous mice showing a normal phenotype and are fertile, whereas new born mouse of Dub-2−/− homozygous alleles could not survive. In addition, Dub-2−/− embryo could not be seen between E6.5 and E12.5 stages. Furthermore, the number of embryos showing normal embryonic development for further stages is decreased in heterozygotes. Even embryonic stem cells from inner cell mass of Dub-2−/− embryos could not be established.ConclusionsOur study suggests that the targeted disruption of Dub-2 may cause embryonic lethality during early gestation, possibly due to the failure of cell proliferation during hatching process.
Highlights
Ubiquitination and deubiquitination are important for posttranslational modification and responsible for many intracellular processes, including cell cycle progression, transcriptional activation and signal transduction [1,2,3]
Our study suggests that the targeted disruption of Dub-2 may cause embryonic lethality during early gestation, possibly due to the failure of cell proliferation during hatching process
Generation of Dub-2 Mutant Mice To investigate the physiological roles of Dub-2 in mouse, we generated Dub-2 knock-out mice
Summary
Ubiquitination and deubiquitination are important for posttranslational modification and responsible for many intracellular processes, including cell cycle progression, transcriptional activation and signal transduction [1,2,3]. Conclusions: Our study suggests that the targeted disruption of Dub-2 may cause embryonic lethality during early gestation, possibly due to the failure of cell proliferation during hatching process.
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