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Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver
Author(s) -
Ichihara Toshiaki,
Komagata Yoshinori,
Yang XiaoLi,
Uezato Tadayoshi,
Enomoto Katsuhiko,
Koyama Kenji,
Miyazaki Junichi,
Sugiyama Toshihiro,
Miura Naoyuki
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.23077
Subject(s) - carcinogenesis , transgene , genetically modified mouse , biology , retinoblastoma , cancer research , hbx , gene , hepatocyte , enhancer , hepatocyte nuclear factor 4 , microbiology and biotechnology , transfection , gene expression , transcription factor , in vitro , genetics , nuclear receptor
Previously, retinoblastoma (Rb) transgenic mice were produced under the control of the Rb gene promoter and showed dwarf characteristics. Here, we created transgenic mice, in which the human Rb gene was controlled by the hepatocyte nuclear factor‐1 gene promoter/enhancer and was expressed primarily in the liver. The liver of these novel transgenic mice was normally developed. Intriguingly, these mice showed resistance to fulminant hepatitis induced by anti‐Fas antibody as well as resistance to chemical carcinogenesis in the liver. These results show that the Rb protein acts as an anti‐apoptotic and anti‐oncogenic agent in vivo . Our novel construct may be useful as a gene cassette in gene therapy for prevention of fulminant hepatitis and hepatoma.