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Production and Characterization of a Transgenic Mouse Model of Human Liver Cancer  

Li, Zhong-Shu (Department of Animal Science, College of Agriculture, Yanbian University)
Lee, Jung-Woong (Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology(KRIBB))
Hyun, Byung-Hwa (Disease Model Research Center, Korea Research Institute of Bioscience & Biotechnology(KRIBB))
Lee, Chul-Ho (Disease Model Research Center, Korea Research Institute of Bioscience & Biotechnology(KRIBB))
Jeong, Kyu-Shick (Disease Model Research Center, Korea Research Institute of Bioscience & Biotechnology(KRIBB))
Fang, Nan-Zhu (Department of Animal Science, College of Agriculture, Yanbian University)
Yeom, Young-Il (Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology(KRIBB))
Publication Information
Reproductive and Developmental Biology / v.31, no.3, 2007 , pp. 145-152 More about this Journal
Abstract
Transgenic mice were generated by microinjecting a plasmid DNA containing the SV40 (simian virus 40) large T antigen (Tag) gene fused with mouse albumin promoter/enhancer sequences into fertilized one-cell mouse embryos. Among eleven founder transgenic animals, four developed hepatocellular carcinoma, two showed kidney cancer and one developed skin and brain tumors. Three stable transgenic lines, #1-2, #1-6 and #1-11 were established. Members of the lines #1-6 and #1-11 reproducibly developed liver tumors by 8 to 10 weeks of age but did not exhibit any phenotypic changes in other tissues. Histological changes loading to liver tumor formation occurred with predictable kinetics and could be classified into three distinct stages; (a) newborn to 3 weeks of age, characterized by hyperplastic hepatocytes with reduced amounts of cytoplasm without any nuclear alterations, (b) between 4 to 8 weeks of age, characterized by diffuse liver cell dysplasia without observable tumor nodules, and (c) 9 weeks of age and thereafter, characterized by hepatocellular carcinomas in the background of extensive liver dysplasia. Metastasis to the lung from a liver carcinoma was observed in #1-11 founder animal. This transgenic mouse system displays similarities with human liver cancers in a number of aspects and provides a useful model for the study of molecular events involved in hepatocarcinogenesis.
Keywords
Transgenic mouse; SV40 Tag; Hepatocellular carcinoma;
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