High bone mass gene of 11q13.3

Abstract

The present invention relates to methods and materials used to isolate and detect a high bone mass gene and a corresponding wild-type gene, and mutants thereof. The present invention also relates to the high bone mass gene, the corresponding wild-type gene, and mutants thereof. The genes identified in the present invention are implicated in bone development. The invention also provides nucleic acids, including coding sequences, oligonucleotide primers and probes, proteins, cloning vectors, expression vectors, transformed hosts, methods of developing pharmaceutical compositions, methods of identifying molecules involved in bone development, and methods of diagnosing and treating diseases involved in bone development. In preferred embodiments, the present invention is directed to methods for treating, diagnosing and preventing osteoporosis.

1 . (canceled)  
     
     
         2 . A method of identifying a molecule involved in bone modulation comprising identifying a molecule that binds to Zmax1, HBM, or both Zmax1 and HBM.  
     
     
         3 . The method of  claim 2 , wherein said molecule is a protein.  
     
     
         4 - 9 . (canceled)  
     
     
         10 . A method of testing a candidate protein for bone modulation activity comprising immobilizing an HBM protein, Zmax1 protein or a combination thereof, exposing the candidate protein to the immobilized protein, and measuring the extent of binding.  
     
     
         11 . The method of  claim 10 , wherein the candidate protein is ApoE.  
     
     
         12 . A method of pharmaceutical development for treating of bone development disorders comprising identifying a molecule that binds to the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or both.  
     
     
         13 . The method of  claim 12 , wherein the molecule inhibits or enhances the function of the amino acid.  
     
     
         14 - 25 . (canceled)  
     
     
         26 . A method for identification of a candidate molecule involved in bone modulation comprising identifying a first molecule that binds to Zmax1, HBM, or both Zmax1 and HBM, and identifying a second molecule that inhibits binding of the first molecule to Zmax1, HBM or both Zmax1 and HBM, wherein the candidate molecule is the second molecule.  
     
     
         27 . A method for identification of a candidate molecule involved in bone modulation comprising: 
 (A) identifying a first molecule that binds to, or that inhibits binding of a second molecule, to either (i) Zmax1 or (ii) a HBM;    (B) measuring the binding of the first molecule, or inhibition of the binding of the second molecule, to the other of either (i) Zmax1 or (ii) HBM; and,    (c) comparing the extent of binding of the first molecule, or the extent of inhibition of binding the second molecule, to each of Zmax1 and HBM, wherein the molecule that binds, or inhibits binding, more or less to HBM versus Zmax1 is the candidate molecule.    
     
     
         28 . The method of  claim 2 , wherein the HBM and/or Zmax1 is in solution.  
     
     
         29 . The method of  claim 2 , wherein the HBM and/or Zmax1 is affixed to a solid support.  
     
     
         30 . The method of  claim 2 , wherein the HBM and/or Zmax1 is located on a cell surface.  
     
     
         31 . The method of  claim 2 , wherein the HBM and/or Zmax1 is expressed by a host cell.  
     
     
         32 . The method of  claim 2 , wherein the molecule which binds to HBM and/or Zmax1 is identified by assaying the competitive binding of the molecule to HBM and/or Zmax1 in the presence of a known ligand.  
     
     
         33 . The method of  claim 2 , wherein the molecule is identified by co-immunoprecipitation with HBM and/or Zmax1.  
     
     
         34 . The method of  claim 2 , wherein the molecule is identified by co-fractionation with HBM and/or Zmax1.  
     
     
         35 . The method of  claim 2 , wherein the molecule is identified by a two-hybrid system in which the extracellular domain of HBM or Zmax1 is encoded on a bait vector.  
     
     
         36 . The method of  claim 2 , wherein the step of identifying a molecule that binds to, HBM and/or Zmax1 is a step of identifying a molecule that binds to HBM.  
     
     
         37 . The method of  claim 2 , wherein the step of identifying a molecule that binds to HBM and/or Zmax1 is a step of identifying a molecule that binds to Zmax1.  
     
     
         38 . The method of  claim 2  wherein the step of identifying a molecule that binds to HBM and/or Zmax1 is a step of identifying a molecule that binds to HBM and to Zmax1.  
     
     
         39 . The method of  claim 26 , wherein the HBM and/or Zmax1 is in solution.  
     
     
         40 . The method of  claim 26 , wherein the HBM and/or Zmax1 is affixed to a solid support.  
     
     
         41 . The method of  claim 26 , wherein the HBM and/or Zmax1 is located on a cell surface.  
     
     
         42 . The method of  claim 26 , wherein the HBM and/or Zmax1 is expressed by a host cell.  
     
     
         43 . The method of  claim 26 , wherein the extracellular domain of HBM or Zmax1 is encoded on a bait vector in a two-hybrid system.  
     
     
         44 . The method of  claim 26 , wherein the step of identifying a second molecule that inhibits binding of a first molecule to HBM and/or Zmax1 is a step of identifying a molecule that inhibits binding of the first molecule to HBM.  
     
     
         45 . The method of  claim 26 , wherein the step of identifying a second molecule that inhibits binding of a first molecule to HBM and/or Zmax1 is a step of identifying a molecule that inhibits binding of the first molecule to Zmax1.  
     
     
         46 . The method of  claim 26 , wherein the step of identifying a second molecule that inhibits binding of a first molecule to HBM and/or Zmax1 is a step of identifying a molecule that inhibits binding of the first molecule to HBM and Zmax1.