Premium
Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice
Author(s) -
Croquelois Adrien,
Blindenbacher Alex,
Terracciano Luigi,
Wang Xueya,
Langer Igor,
Radtke Freddy,
Heim Markus H.
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20571
Subject(s) - alagille syndrome , jag1 , notch signaling pathway , conditional gene knockout , cre recombinase , transgene , biology , gene targeting , genetically modified mouse , gene knockout , phenotype , hyperplasia , microbiology and biotechnology , embryonic stem cell , knockout mouse , bile duct , recombinase , cre lox recombination , cell growth , cancer research , gene , signal transduction , cholestasis , endocrinology , medicine , genetics , recombination
The discovery that the human Jagged1 gene ( JAG1 ) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon‐inducible Cre ‐recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion , within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver. (H EPATOLOGY 2005;41:487–496.)