Inducible cancer model to study the molecular basis of host tumor cell interactions in vivo

Abstract

A non-human mammal having incorporated into its genome an expression construct in which nucleic acid encoding and oncogene is operably linked to an inducible promoter; the mammal further has a genetic mutation that causes it to have an increased susceptibility to cancer.

1 . A non-human mammal having incorporated into its genome an expression construct comprising nucleic acid encoding an oncogene operably linked to an inducible promoter, said mouse further comprising a genetic mutation that causes said mammal to have greater susceptibility to cancer than a mammal not comprising said mutation.  
   
   
       2 . The mammal of  claim 1 , wherein said mammal is a mouse.  
   
   
       3 . The mammal of  claim 1 , wherein said oncogene is ras.  
   
   
       4 . The mammal of  claim 3 , wherein said ras has an activating mutation.  
   
   
       5 . The mammal of  claim 1 , wherein said inducible promoter can be induced by doxycycline.  
   
   
       6 . The mammal of  claim 1 , wherein said mutation is in DNA encoding a tumor suppressor.  
   
   
       7 . The mammal of  claim 6 , wherein said tumor suppressor is INK4.  
   
   
       8 . A non-human mammal having incorporated into its genome: (i) a first expression construct comprising a reverse tetracycline transactivator operably linked to a tissue-specific promoter; and (ii) a second expression construct comprising nucleic acid encoding an oncogene operably linked to a promoter that can be regulated by said reverse tetracycline transactivator, said mammal further comprising a genetic mutation that causes said mammal to have greater susceptibility to cancer than a mammal not comprising said mutation.  
   
   
       9 . The mammal of  claim 8 , wherein said tissue-specific promoter is a tyrosinase promoter.  
   
   
       10 . The mammal of  claim 8 , wherein expression of said oncogene results in said mammal having greater susceptibility to cancer than a mammal comprising said mutation but not expressing said oncogene.  
   
   
       11 . A non-human mammal having incorporated into its genome: (i) a first expression construct comprising a reverse tetracycline transactivator operably linked to a tyrosinase promoter; and (ii) a second expression construct comprising nucleic acid encoding ras operably linked to a promoter that can be regulated by said reverse tetracycline transactivator.