title: The nuclear pore complex protein Elys is required for genome stability in mouse intestinal epithelial progenitor cells.
abstract: OBJECTIVE
  Elys is a conserved protein that directs nuclear pore complex (NPC) assembly in mammalian cell lines and developing worms and zebrafish. Related studies in these systems indicate a role for Elys in DNA replication and repair. Intestinal epithelial progenitors of zebrafish elys mutants undergo apoptosis early in development. However, it is not known whether loss of Elys has a similar effect in the mammalian intestine or whether the NPC and DNA repair defects each contribute to the overall phenotype.
  
  
  METHODS
  We developed mice in which a conditional Elys allele was inactivated in the developing intestinal epithelium and during preimplantation development. Phenotypes of conditional mutant mice were determined using immunohistochemical analysis for nuclear pore proteins, electron microscopy, and immunoblot analysis of DNA replication and repair proteins.
  
  
  RESULTS
  Conditional inactivation of the Elys locus in the developing mouse intestinal epithelium led to a reversible delay in growth in juvenile mice that was associated with epithelial architecture distortion and crypt cell apoptosis. The phenotype was reduced in adult mutant mice, which were otherwise indistinguishable from wild-type mice. All mice had activated DNA damage responses but no evidence of NPC assembly defects.
  
  
  CONCLUSIONS
  In mice, Elys maintains genome stability in intestinal epithelial progenitor cells, independent of its role in NPC assembly in zebrafish.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.forename: Gangarao
authors.initials: G
authors.lastname: Davuluri
authors.forename: Weilong
authors.initials: W
authors.lastname: Gong
authors.forename: Christoph
authors.initials: C
authors.lastname: Seiler
authors.forename: Kristin
authors.initials: K
authors.lastname: Lorent
authors.forename: Emma E
authors.initials: EE
authors.lastname: Furth
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.forename: Michael
authors.initials: M
authors.lastname: Pack
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D004260:DNA Repair / Q000235:genetics; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D042822:Genomic Instability; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D022022:Nuclear Pore / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish
chemical_list: C466200:ELYS protein, mouse; D014157:Transcription Factors; D012313:RNA