Non-human transgenic animal models for hepatocellular carcinoma

Abstract

The invention relates to the field of non-human, transgenic animal models for hepatocellular carcinoma.

1 . A transgenic mammal whose genome comprises a stably integrated transgenic nucleotide sequence encoding an FGF19 operably linked to a promoter.  
     
     
         2 . The transgenic mammal of  claim 1 , wherein said mammal is a mouse.  
     
     
         3 . The transgenic mammal of  claim 1 , wherein said FGF19 is expressed in skeletal muscle.  
     
     
         4 . The transgenic mammal of  claim 1 , wherein said mammal acquires hepatic disease.  
     
     
         5 . The transgenic mammal of  claim 4 , wherein said disease is hepatocellular carcinoma.  
     
     
         6 . The transgenic mammal of  claim 1 , wherein said mammal serves as an animal model for the study and development of treatments for said hepatocellular carcinoma.  
     
     
         7 . The transgenic mammal of  claim 1 , wherein said mammal has elevated levels of alpha-fetoprotein.  
     
     
         8 . The transgenic mammal of  claim 1 , wherein said mammal exhibits increased proliferation of pericentral hepatocytes as compared with a control, non-transgenic mammal.  
     
     
         9 . An isolated cell from the mammal of  claim 1 , wherein said cell expresses said FGF19.  
     
     
         10 . A method for screening for biologically active agents that modulate a phenomenon associated with hepatocellular carcinoma, the method comprising: 
 combining a candidate agent with a transgenic mammal having a genome comprising a stably integrated transgene encoding FGF19 operably linked to a promoter, wherein said transgene results in said mammal acquiring hepatocellular carcinoma; and    determining the effect of said agent on the hepatocellular carcinoma of said mammal.    
     
     
         11 . A method for screening for biologically active agents that modulate a phenomenon associated with hepatocellular carcinoma, the method comprising: 
 combining a candidate agent with a transgenic mammal cell culture, each cell of said culture comprising a stably integrated transgene encoding FGF19 operably linked to a promoter, wherein said transgene results in said mammal acquiring hepatocellular carcinoma; and    determining the effect of said agent on the transgenic mammal cell culture.    
     
     
         12 - 178 . (canceled)