Chugai Seiyaku Kabushiki Kaisha

Tokyo Metropolitan Institute of Medical Science

Phoenixbio Co., Ltd.

Koichi Jishage

Michinori Kohara

Yasuko Kinoshita

Takahiro Ishiguro

Chise Mukaidani

Yosuke Kawase

Satoko Hamamura

Hiroki Oshita

Otoya Ueda

Naoko Wada

Hiroshi Hino

Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Gene-modified mouse expressing human GPC3 polypeptide

The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3&#x3b5;, CD3&#x3b4;, and CD3&#x3b3; in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3&#x3b5;, CD3&#x3b4;, and CD3&#x3b3;. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.

Non-human animal having human CD3 gene substituted for endogenous CD3 gene

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 non-human animal in which a DNA comprising an hp7 sequence-encoding DNA and a poly A addition signal-encoding DNA added on the 3' side of a DNA encoding an arbitrary foreign gene is inserted in the same reading frame as that of an arbitrary target gene present on the genome of the non-human animal.

Gene knock-in non-human animal

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.

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Gotemba, Japan

Koichi Jishage