Transgenic tieg non-human animals

Abstract

Materials and Methods related to a transgenic non-human animal (e.g., a transgenic non-human mammal) whose genome comprises a disrupted TIEG allele are provided. Methods for making such transgenic non-human animals, and using them to identify and characterize agents that affect conditions related to TIEG activity, such as cardiac hypertrophy and bone formation also are provided. In addition, materials and methods related to the treatment of hypertrophic cardiomyopathy are provided.

1 . A method for determining whether or not a test compound is a potential treatment compound for human hypertrophic cardiomyopathy, said method comprising:
 (a) administering said test compound to a male TIEG −/− mouse, and   (b) determining whether or not said mouse develops symptoms of human hypertrophic cardiomyopathy to a lesser degree than those developed in a control male TIEG −/− mouse not receiving said test compound, wherein a lesser degree of symptoms of human hypertrophic cardiomyopathy in said mouse indicates that said test compound is a potential treatment compound for human hypertrophic cardiomyopathy.   
     
     
         2 . The method of  claim 1 , wherein said test compound is an siRNA or antisense oligo that reduces the expression of a PTTG-1 polypeptide. 
     
     
         3 . A method for treating hypertrophic cardiomyopathy in a mammal, said method comprising administering a molecule to said mammal under conditions wherein the severity of a symptom of hypertrophic cardiomyopathy is reduced in said mammal, wherein said molecule reduces expression of a PTTG-1 polypeptide in said mammal or inhibits a PTTG-1 polypeptide activity in said mammal. 
     
     
         4 . The method of  claim 3 , wherein said mammal is a human. 
     
     
         5 . The method of  claim 3 , wherein said molecule is an siRNA or antisense oligo that reduces the expression of a PTTG-1 polypeptide. 
     
     
         6 . The method of  claim 3 , wherein said molecule reduces a PTTG-1 polypeptide activity. 
     
     
         7 . The method of  claim 3 , wherein said molecule is TGFβ, EGF, BMP-2, BMP-6, or estrogen.