Urokinase-type plasminogen activator transgenic mouse

A chimeric mouse, which has a chimeric liver containing human hepatocytes, wherein human hepatocytes account for at least 10% of all hepatocytes in the chimeric liver, obtained by:

• transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes uPA operably linked under the control thereof;
• injecting the transformed mouse ES cells obtained above into a host embryo;
• transplanting the host embryo obtained above via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse;
• crossing the chimeric mice obtained above, so as to obtain a transgenic mouse with liver damage in which the DNA fragment is introduced in a heterozygous form, wherein the serum ALT level increases at least from when it is 6 weeks old to when it is 8 weeks old;
• crossing the mouse with liver damage with an immunodeficient mouse forming an immunodeficient mouse with liver damage having the uPA gene in a heterozygous form;
• and
• transplanting human hepatocytes into the immunodeficient mouse with liver damage having the uPA gene in a heterozygous form.