a) inserting an exogenous gene of interest into a suitable vector carrying sequences homologous to a target site, to construct a recombinant targeting vector; b) transfecting ES cells of a studied animal using said targeting vector from step a), and screening targeted ES cells which have integrated the exogenous gene into a specific site; c) injecting targeted ES cells obtained from step b) into said animal"s blastulas and culturing the blastulas in vitro, so that embryos containing targeted ES cells are generated; and d) implanting embryos generated from step c) into said animal"s uterus, thereby progeny expressing the exogenous gene stably is developed. The invention fiirther relates to the use of said transgenic mouse in research of hepatocellular carcinoma pathogenesis, its early stage diagnosis and therapy, and screening of anticancer drugs.
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