Sgrf gene-modified non-human animals

Abstract

A targeting vector was constructed by replacing exon regions in the SGRF gene with appropriate drug marker genes. This vector was transfected into mouse ES cell lines to obtain chimeric mice, which were then crossed with C57BL/6J mice to obtain mice comprising cells in which one SGRF gene alleles was inactivated. By crossing these mice with each other, the present inventors succeeded in producing mice in which both SGRF gene alleles were inactivated. These genetically modified animals can be used to predict the side effects of drugs such as SGRF antagonists.

1 . A genetically modified non-human animal in which SGRF gene expression is artificially suppressed.  
     
     
         2 . A genetically modified non-human animal in which a foreign gene is inserted into one or both of the SGRF gene alleles.  
     
     
         3 . The genetically modified animal of  claim 1 , in which the non-human animal is a rodent.  
     
     
         4 . The genetically modified animal of  claim 3 , in which the rodent is a mouse.  
     
     
         5 . A cell line established from a genetically modified animal of  claim 1 .  
     
     
         6 . A method for producing an anti-SGRF antibody, wherein the method comprises using a genetically modified animal of  claim 1 .  
     
     
         7 . A non-human ES cell in which SGRF gene expression is artificially suppressed.  
     
     
         8 . A non-human ES cell in which a foreign gene is inserted into one or both of the SGRF gene alleles.  
     
     
         9 . The ES cell of  claim 7 , in which the non-human ES cell is a rodent ES cell.  
     
     
         10 . The ES cell of  claim 9 , in which the rodent ES cell is a mouse ES cell.  
     
     
         11 . An infection-preventing agent, comprising a compound that can substitute for SGRF or a SGRF signal, as its active ingredient.  
     
     
         12 . A therapeutic agent for autoimmune diseases, which comprises an SGRF antagonist as its active ingredient.  
     
     
         13 . A therapeutic agent for inflammatory diseases, which comprises an SGRF antagonist as its active ingredient.  
     
     
         14 . The therapeutic agent of  claim 12 , in which the antagonist is an anti-SGRF antibody.  
     
     
         15 . A method of screening for a compound as a candidate for a therapeutic agent for autoimmune or inflammatory diseases, wherein the method comprises the steps of (a) to (c): 
 (a) contacting SGRF with a test compound;    (b) measuring the binding activity of SGRF with a test compound;    (c) selecting a compound which binds to SGRF.    
     
     
         16 . A method of screening for a compound which can substitute for SGRF protein function, wherein the method comprises the steps of (a) to (c): 
 (a) administering a test compound into a genetically modified animal of  claim 1;     (b) determining whether the test compound can substitute for SGRF function;    (c) selecting a compound that can substitute for SGRF function.    
     
     
         17 . The genetically modified animal of  claim 2 , in which the non-human animal is a rodent.  
     
     
         18 . The genetically modified animal of  claim 17 , in which the rodent is a mouse.  
     
     
         19 . A cell line established from a genetically modified animal of  claim 2 .  
     
     
         20 . A method for producing an anti-SGRF antibody, wherein the method comprises using a genetically modified animal of  claim 2 .  
     
     
         21 . The ES cell of  claim 8 , in which the non-human ES cell is a rodent ES cell.  
     
     
         22 . The ES cell of  claim 21 , in which the rodent ES cell is a mouse ES cell.  
     
     
         23 . The therapeutic agent of  claim 13 , in which the antagonist is an anti-SGRF antibody.  
     
     
         24 . A method of screening for a compound which can substitute for SGRF protein function, wherein the method comprises the steps of (a) to (c): 
 (a) administering a test compound into a genetically modified animal of  claim 2;     (b) determining whether the test compound can substitute for SGRF function;    (c) selecting a compound that can substitute for SGRF function.