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Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c‐ jun in the liver
Author(s) -
Behrens Axel,
Sibilia Maria,
David JeanPierre,
MöhleSteinlein Uta,
Tronche François,
Schütz Günther,
Wagner Erwin F.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.7.1782
Subject(s) - liver regeneration , hepatocyte , c jun , biology , cell growth , endocrinology , microbiology and biotechnology , regeneration (biology) , hepatectomy , medicine , transcription factor , gene , genetics , in vitro , surgery , resection
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.