Compositions for diagnosis and therapy of diseases associated with aberrant expression of futrins (r-spondins) and/or wnt

Abstract

The present invention relates to a composition useful for the diagnosis of diseases associated with aberrant expression of the genes encoding the secreted proteins Futrin 1, 2, 3 and/or 4(=R-Spondin 2, 3, 1 and 4, respectively), e.g. in connection with tumors or diseases of the muscle, kidneys or bones. The present invention also relates to a pharmaceutical composition containing a compound which is capable of modifying (a) the expression of the gene encoding Futrin 1, 2, 3 and/or 4 or (b) the activity of the Futrin 1, 2, 3 and/or 4 protein.

1 - 20  (canceled) 
     
     
         21 . A method for determining whether an anti-Futrin 2 antibody inhibits Wnt signaling comprising the steps of
 (a) providing a mammalian cell in culture comprising a Futrin 2 polypeptide and a Wnt inducible reporter, wherein the Futrin 2 polypeptide comprises the amino acid sequence of SEQ ID NO:27, the amino acid sequence of amino acids 21-272 of SEQ ID NO:27, the amino acid sequence of amino acids 1-149 of SEQ ID NO:27, or the amino acid sequence of amino acids 21-149 of SEQ ID NO:27,   (b) contacting the cell with a monoclonal antibody that binds Futrin 2 polypeptide, and   (c) detecting the level of reporter expression in the cell in the presence and absence of the antibody, wherein a decrease in the level of reporter expression in the presence of the antibody indicates that the antibody is an antagonist of Wnt signaling.   
     
     
         22 . The method of  claim 21 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 21-149 of SEQ ID NO:27. 
     
     
         23 . The method of  claim 21 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 21-272 of SEQ ID NO:27. 
     
     
         24 . The method of  claim 21 , wherein the Futrin 2 polypeptide comprises SEQ ID NO:27. 
     
     
         25 . The method of  claim 21 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 1-149 of SEQ ID NO:27. 
     
     
         26 . The method of  claim 21 , wherein the antibody is an antibody fragment. 
     
     
         27 . The method of  claim 21 , wherein the antibody fragment is a Fab fragment or F(ab′)2. 
     
     
         28 . The method of  claim 21 , wherein the antibody binds at least one of the furin-like domains 1 and 2 of SEQ ID NO:27. 
     
     
         29 . The method of  claim 28 , wherein the antibody is an antibody fragment. 
     
     
         30 . The method of  claim 29 , wherein the antibody fragment is a Fab fragment or F(ab′)2. 
     
     
         31 . The method of  claim 21 , wherein the antibody is labeled with a detectable label. 
     
     
         32 . The method of  claim 31 , wherein the detectable label is a radioisotope or enzyme label.