Abstract: An object of the present invention is to provide human fatty-liver model cells showing symptoms of the hepatic tissue of fatty liver. The present invention relates to human fatty-liver model cells, which are produced by culturing human hepatocytes derived from fatty liver in a medium containing dimethyl sulfoxide.

Abstract: 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.

Abstract: 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.

Abstract: Provided is a non-human animal that is highly practical as a hyperuricenia model, the non-human animal being the following: (a) a non-human animal obtained by producing a primary chimeric non-human animal by transplantation of human hepatocytes to an immunodeficient non-human animal with liver dysfunction; and subsequently administering a purine base-containing substance to the primary chimeric non-human animal, or (b) a non-human animal obtained by producing a serially transplanted chimeric non-human animal via two steps, a first step being a step of producing a primary chimeric non-human animal by transplantation of human hepatocytes to an immunodeficient non-human animal with liver dysfunction, a second step being a step of transplanting the human hepatocytes grown in the body of the primary chimeric non-human animal to an immunodeficient non-human animal with liver dysfunction, the second step being performed one or more times; and subsequently administering a purine base-containing substance to the seri

Abstract: 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.

Abstract: Provided is a non-human animal that is highly practical as a hyperuricenia model, the non-human animal being the following: (a) a non-human animal obtained by producing a primary chimeric non-human animal by transplantation of human hepatocytes to an immunodeficient non-human animal with liver dysfunction; and subsequently administering a purine base-containing substance to the primary chimeric non-human animal, or (b) a non-human animal obtained by producing a serially transplanted chimeric non-human animal via two steps, a first step being a step of producing a primary chimeric non-human animal by transplantation of human hepatocytes to an immunodeficient non-human animal with liver dysfunction, a second step being a step of transplanting the human hepatocytes grown in the body of the primary chimeric non-human animal to an immunodeficient non-human animal with liver dysfunction, the second step being performed one or more times; and subsequently administering a purine base-containing substance to the seri

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A polynucleotide encoding the amino acid shown in SEQ ID NO:2 or SEQ ID NO: 5, or encoding an amino acid sequence having not less than 98% identity thereto; preferably a polynucleotide comprising replacement of the amino acid corresponding to glutamic acid at position 1202 of SEQ ID NO:2 (position 177 of SEQ ID NO:5) with glycine, replacement of the amino acid corresponding to glutamic acid at position 1056 (position 31 of SEQ ID NO:5) with valine, and replacement of the amino acid corresponding to alanine at position 2199 (position 1174 of SEQ ID NO:5) with threonine.

Abstract: A polynucleotide encoding the amino acid shown in SEQ ID NO:2 or SEQ ID NO: 5, or encoding an amino acid sequence having not less than 98% identity thereto; preferably a polynucleotide comprising replacement of the amino acid corresponding to glutamic acid at position 1202 of SEQ ID NO:2 (position 177 of SEQ ID NO:5) with glycine, replacement of the amino acid corresponding to glutamic acid at position 1056 (position 31 of SEQ ID NO:5) with valine, and replacement of the amino acid corresponding to alanine at position 2199 (position 1174 of SEQ ID NO:5) with threonine.

Abstract: Disclosed is a nonhuman animal showing the symptoms of human nonalcoholic steatohepatitis which is obtained by transplanting human hepatocytes into an immunodeficient hepatopathic nonhuman animal to produce a chimeric nonhuman animal and then transplanting human hepatocytes that are propagated in the body of the chimeric nonhuman animal into an immunodeficient hepatopathic nonhuman animal of the same species as the immunodeficient hepatopathic nonhuman animal described above, as well as a nonhuman animal showing the symptoms of human fatty liver which is obtained by transplanting human hepatocytes into an immunodeficient hepatopathic nonhuman animal to produce a chimeric nonhuman animal.

Abstract: A polynucleotide encoding the amino acid shown in SEQ ID NO:2 or SEQ ID NO: 5, or encoding an amino acid sequence having not less than 98% identity thereto; preferably a polynucleotide comprising replacement of the amino acid corresponding to glutamic acid at position 1202 of SEQ ID NO:2 (position 177 of SEQ ID NO:5) with glycine, replacement of the amino acid corresponding to glutamic acid at position 1056 (position 31 of SEQ ID NO:5) with valine, and replacement of the amino acid corresponding to alanine at position 2199 (position 1174 of SEQ ID NO:5) with threonine.

Abstract: A method for culture of hair follicular dermal sheath cells or precursor cells thereof which are potent cellular materials for such as hair regeneration by cell transplantation is provided. That is, by performing culture in an animal cell culture medium supplemented with platelet-derived growth factor AA (PDGF-AA) and fibroblast growth factor 2 (FGF2), hair follicular dermal sheath cells are proliferated while sustaining their function, or hair follicular dermal sheath precursor cells are differentiated into dermal sheath cells and proliferated.

Abstract: The invention provides a method for precisely predicting the metabolism of a drug in human liver and the effect of the drug on liver function. The invention provides a method for predicting a metabolite of a test substance produced in human liver and functions of the liver, wherein the method includes administering a test substance to a nonhuman chimeric animal and a non-chimeric animal of the same species, wherein the chimeric animal intracorporeally carries a population of human-origin hepatocytes having proliferation potential and in which the hepatocyte, population substantially functions as the liver of the chimeric animal, and wherein these animals are protected from the attack by a human complement produced by the hepatocytes; and analyzing and comparing metabolites from the chimeric animal and the non-chimeric animal.