Phoenixbio Co., Ltd.

Chugai Seiyaku Kabushiki Kaisha

Tokyo Metropolitan Institute of Medical Science

Tottori University

National University Corporation Tottori University

Satoko Hamamura

Chise Mukaidani

Michinori Kohara

Koichi Jishage

Yosuke Kawase

Hiroki Oshita

Mitsuo Oshimura

Yasuhiro Kazuki

Kota Kato

Masakazu Kakuni

Takashi Shimada

Hidetaka Kamimura

Akio Kawamura

Naoyuki Nakada

Masato Ohbuchi

The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of:

Urokinase-type plasminogen activator transgenic mouse

The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

A chimeric non-human animal having an in vivo human hepatocyte population, wherein the effects of non-human animal cells on drug metabolism are suppressed or deleted is provided. A method for producing a chimeric non-human animal that lacks a drug-metabolizing system or has a suppressed drug-metabolizing system and is provided with a drug-metabolizing system driven by human hepatocytes, is provided. The method comprises transplanting human hepatocytes into a non-human animal characterized by (i) being immunodeficient, (ii) having liver damage, and (iii) lacking the functions of an endogenous Cyp3a gene.

Chimeric non-human animal carrying human hepatocyte

Growing community of inventors

Higashihiroshima, Japan

Satoko Hamamura