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  • The EMBO Journal (2002) 21, 1782 - 1790
  • doi:10.1093/emboj/21.7.1782

Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver

Axel Behrens1,2,5, Maria Sibilia1,3,5, Jean-Pierre David1, Uta Möhle-Steinlein1, François Tronche4, Günther Schütz4 and Erwin F. Wagner1

  1. Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, A-1030 Vienna, Austria
  2. Present address: Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
  3. Present address: Department of Dermatology, VIRCC BMT, University of Vienna Medical School, Brunnerstrasse 59, 1235 Vienna, Austria
  4. Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany
  5. A.Behrens and M.Sibilia contributed equally to this work.

Correspondence to:

Erwin F. Wagner, E-mail: Wagner@nt.imp.univie.ac.at

Received 13 November 2001; Accepted 5 February 2002; Revised 1 February 2002

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 G1–S phase progression. These studies identify c-Jun as a critical regulator of hepatocyte proliferation and survival during liver development and regeneration.

  • Keywords:

    • AP-1,
    • c-jun,
    • hepatocyte growth factor,
    • liver regeneration