title: Embryonic demise caused by targeted disruption of a cysteine protease Dub-2.
abstract: BACKGROUND
  A 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.
  
  
  RESULTS
  To 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.
  
  
  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.
authors.affiliation: Department of Biomedical Science, CHA Stem Cell Institute, CHA University, CHA General Hospital, Gyeonggi-Do, Republic of Korea. baek@cha.ac.kr
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Heyjin
authors.initials: H
authors.lastname: Lee
authors.forename: Sunmee
authors.initials: S
authors.lastname: Yang
authors.forename: Soo-Bin
authors.initials: SB
authors.lastname: Lim
authors.forename: Wonwoo
authors.initials: W
authors.lastname: Lee
authors.forename: Jeoung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lim
authors.forename: Kisun
authors.initials: K
authors.lastname: Jun
authors.forename: Dong-Ryul
authors.initials: DR
authors.lastname: Lee
authors.forename: Young
authors.initials: Y
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis; D053624:Blastocyst Inner Cell Mass / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D020964:Embryo Loss / Q000201:enzymology* / Q000473:pathology*; D047108:Embryonic Development; D010450:Endopeptidases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005307:Fertilization in Vitro; D017353:Gene Deletion; D018390:Gene Targeting; D060005:Genotyping Techniques; D006579:Heterozygote; D017874:Immediate-Early Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D013081:Sperm Motility; D013094:Spermatozoa / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
chemical_list: D017874:Immediate-Early Proteins; C103857:Dub2 protein, mouse; D010450:Endopeptidases