title: Ubp43 gene expression is required for normal Isg15 expression and fetal development.
abstract: BACKGROUND
  Isg15 covalently modifies murine endometrial proteins in response to early pregnancy. Isg15 can also be severed from targeted proteins by a specific protease called Ubp43 (Usp18). Mice lacking Ubp43 (null) form increased conjugated Isg15 in response to interferon. The Isg15 system has not been examined in chorioallantoic placenta (CP) or mesometrial (MM) components of implantation sites beyond 9.5 days post coitum (dpc). It was hypothesized that deletion of Ubp43 would cause disregulation of Isg15 in implantation sites, and that this would affect pregnancy rates.
  
  
  METHODS
  Heterozygous (het) Ubp43 mice were mated and MM and CP implantation sites were collected on 12.5 and 17.5 days post-coitum (dpc).
  
  
  RESULTS
  Free and conjugated Isg15 were greater on 12.5 versus 17.5 dpc in MM. Free and conjugated Isg15 were also present in CP, but did not differ due to genotype on 12.5 dpc. However, null CP had greater free and conjugated Isg15 when compared to het/wt on 17.5 dpc. Null progeny died in utero with fetal genotype ratios (wt:het:null) of 2:5:1 on 12.5 and 2:2:1 on 17.5 dpc. Implantation sites were disrupted within the junctional zone and spongiotrophoblast, contained less vasculature based on lectin B4 staining and contained greater Isg15 mRNA and VEGF protein in Ubp43 null when compared to wt placenta.
  
  
  CONCLUSIONS
  It is concluded that Isg15 and its conjugates are present in implantation sites during mid to late gestation and that deletion of Ubp43 causes an increase in free and conjugated Isg15 at the feto-maternal interface. Also, under mixed genetic background, deletion of Ubp43 results in fetal death.
authors: Department of Animal Science, University of Wyoming, Laramie, Wyoming, 82071, USA. lrempel@kumc.ecu
authors: Lea A
authors: LA
authors: Rempel
authors: Kathleen J
authors: KJ
authors: Austin
authors: Kenneth J
authors: KJ
authors: Ritchie
authors: Ming
authors: M
authors: Yan
authors: Meifeng
authors: M
authors: Shen
authors: Dong-Er
authors: DE
authors: Zhang
authors: Luiz E
authors: LE
authors: Henkes
authors: Thomas R
authors: TR
authors: Hansen
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000235:genetics; D010920:Placenta / Q000033:anatomy & histology / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D043222:Ubiquitin Thiolesterase; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; D014452:Ubiquitins; D010450:Endopeptidases; C118306:Usp18 protein, mouse; D043222:Ubiquitin Thiolesterase