Transgenic non-human animals expressing a gdf-11 dominant negative polypeptide, and methods of making and using same

Abstract

A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-11 (GDF-11) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-11. The animals so treated are characterized by increased muscle tissue and bone tissue.

1 . A method of producing animal food products having an increased number of ribs comprising: 
 a) introducing a transgene disrupting or interfering with expression of growth differentiation factor-11 (GDF-11) into an embryo into germ cells of a pronuclear embryo of the animal;    b) implanting the embryo into the oviduct of a pseudopregnant female thereby allowing the embryo to mature to full term progeny;    c) testing the progeny for presence of the transgene to identify transgene-positive progeny;    d) cross-breeding transgene-positive progeny to obtain further transgene-positive progeny; and    e) processing the progeny to obtain foodstuff.    
     
     
         2 . The method of  claim 1 , wherein the transgene comprises GDF-11 antisense polynucleotides.  
     
     
         3 . The method of  claim 1 , wherein the transgene comprises a gene encoding a dominant negative GDF-11 polypeptide.  
     
     
         4 . A method of producing avian, porcine or bovine food products having an increased number of ribs comprising: 
 a) introducing a transgene disrupting or interfering with expression of growth differentiation factor-11 (GDF-11) into an embryo of an avian, porcine or bovine animal;    b) culturing the embryo under conditions whereby progeny are hatched;    c) testing the progeny for presence of the transgene to identify transgene-positive progeny;    d) cross-breeding transgene-positive progeny; and    e) processing the progeny to obtain foodstuff.    
     
     
         5 . The method of  claim 4 , wherein the transgene comprises GDF-11 antisense polynucleotides.  
     
     
         6 . The method of  claim 4 , wherein the transgene comprises a gene encoding a dominant negative GDF-11 polypeptide.  
     
     
         7 . The transgenic animal of  claim 4 , wherein the transgene comprises a polynucleotide encoding a truncated GDF-11 polypeptide.  
     
     
         8 . A method of treating a chronic or acute renal disease in a subject having such a disease, comprising: 
 administering to the subject, a reagent which affects GDF-11 activity or expression.    
     
     
         9 . The method of  claim 8 , wherein the reagent is an agonist of GDF-11.  
     
     
         10 . The method of  claim 8 , wherein the reagent is an antagonist of GDF-11.  
     
     
         11 . The method of  claim 10 , wherein the antagonist is an antibody to GDF-11.  
     
     
         12 . The method of  claim 10 , wherein the antagonist is an antisense polynucleotide to GDF-11.