title: Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver.
abstract: Mice lacking the AP-1 transcription factor c-jun die at mid-gestation showing heart defects and impaired hepatogenesis. To inactivate c-jun in hepatocytes, mice carrying a floxed c-jun allele were generated. Perinatal liver-specific c-jun deletion caused reduced hepatocyte proliferation and decreased body size. After partial hepatectomy, half of the mutants died and liver regeneration was impaired. This phenotype was not present in mice lacking the N-terminal phosphorylation sites of c-Jun. The failure to regenerate was accompanied by increased cell death and lipid accumulation in hepatocytes. Moreover, cyclin-dependent kinases and several cell cycle regulators were affected, resulting in inefficient G(1)-S phase progression. These studies identify c-Jun as a critical regulator of hepatocyte proliferation and survival during liver development and regeneration.
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Behrens
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: David
authors.forename: Uta
authors.initials: U
authors.lastname: Möhle-Steinlein
authors.forename: François
authors.initials: F
authors.lastname: Tronche
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D005260:Female; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*
chemical_list: D016755:Proto-Oncogene Proteins c-jun