Atopic dermatitis model non-human animal and use thereof

Abstract

An atopic dermatitis model non-human animal, containing a gene mutation in which a complex containing dedicator of cytokinesis 8 (DOCK8) protein, mammalian STE20-like kinase 1 (MST1) protein, and endothelial PAS domain protein 1 (EPAS1) protein is not formed in CD4+ T cells.

1 .- 26 . (canceled) 
     
     
         27 . A method for screening a therapeutic agent for atopic dermatitis, comprising:
 expressing EPAS1 gene in a cell, into which a reporter construct in which a reporter gene is linked downstream of an IL-31 promoter is introduced in the presence of a test substance to quantitatively determine an expression level of the reporter gene,   wherein a decrease of the expression level of the reporter gene when compared to the expression level of the reporter gene in the absence of the test substance indicates that the test substance is the therapeutic agent for atopic dermatitis.   
     
     
         28 . A method for screening a therapeutic agent for atopic dermatitis, comprising:
 expressing EPAS1 gene in T cells, and stimulating TCR of the T cells with anti-CD3ε antibody in the presence of a test substance to quantitatively determine an expression level of IL-31,   wherein a decrease of the expression level of IL-31 when compared to the expression level of IL-31 in the absence of the test substance indicates that the test substance is the therapeutic agent for atopic dermatitis.   
     
     
         29 . A method for screening a therapeutic agent for atopic dermatitis, comprising:
 stimulating TCR of DOCK8 −/−  T cells or MST1 −/−  T cells, into which a reporter construct in which a reporter gene is linked downstream of an IL-31 promoter is introduced in the presence of a test substance to quantitatively determine an expression level of the reporter gene,   wherein a decrease of the expression level of the reporter gene when compared to the expression level of the reporter gene in the absence of the test substance indicates that the test substance is the therapeutic agent for atopic dermatitis.   
     
     
         30 . The method for screening a therapeutic agent for atopic dermatitis according to  claim 29 , wherein the DOCK8 −/−  T cells is DOCK8 −/−  CD4 +  T cells, and the MST1 −/−  T cells is MST1 −/−  CD4 +  T cells. 
     
     
         31 . The method for screening a therapeutic agent for atopic dermatitis according to  claim 30 , wherein the DOCK8 −/−  CD4 +  T cells is DOCK8 −/−  AND Tg CD4 +  T cells or DOCK8 −/−  OTII Tg CD4 +  T cells, and the MST1 −/−  CD4 +  T cells is MST1 −/−  AND Tg CD4 +  T cells or MST1 −/−  OTII Tg CD4 +  T cells. 
     
     
         32 . A method for screening a therapeutic agent for atopic dermatitis, comprising:
 expressing EPAS1 gene in DOCK8 −/−  cells or in MST1 −/−  cells in the presence of a test substance to quantitatively determine the level of nuclear EPAS1 protein,   wherein a decrease of the level of nuclear EPAS1 protein when compared to the level of nuclear EPAS1 protein in the absence of the test substance indicates that the test substance is the therapeutic agent for atopic dermatitis.