Methods for modulating the activity of MSH-5

Abstract

An animal, e.g., transgenic mouse, in which the MSH5 gene is misexpressed. The animal is useful for screening treatments for a number of conditions. Methods for identifying contraceptive agents are also described.

1 . A method for modulating fertility in a subject comprising contacting a subject with a compound selected from the group consisting of an MSH5 peptide, an MSH5 nucleic acid molecule, an antisense MSH5 nucleic acid molecule, an anti-MSH5 antibody, and a naturally-occurring target molecule of an MSH5 protein, in an amount sufficient to modulate MSH5 expression or MSH5 activity, thereby modulating fertility in a subject.  
     
     
         2 . The method of  claim 1 , wherein the expression or activity of MSH5 is inhibited.  
     
     
         3 . The method of  claim 2 , wherein said method is used in contraception.  
     
     
         4 . The method of  claim 1 , wherein said compound is capable of modulating MSH5 expression.  
     
     
         5 . The method of  claim 1 , wherein said compound is capable of modulating MSH5 activity.  
     
     
         6 . The method of  claim 1 , wherein said MSH5 activity is modulation of ovarian meiosis.  
     
     
         7 . The method of  claim 1 , wherein said MSH5 activity is modulation of chromosome pairing.  
     
     
         8 . The method of  claim 1 , wherein said MSH5 activity is modulation of chromosome synapsis.  
     
     
         9 . The method of  claim 1 , wherein said compound comprises the nucleic acid molecule shown in  FIG. 1A  or a fragment thereof.  
     
     
         10 . A method for preventing fertilization in a subject comprising administering to a subject a compound selected from the group consisting of an MSH5 peptide, an MSH5 nucleic acid molecule, an antisense MSH5 nucleic acid molecule, an anti-MSH5 antibody, and a naturally-occurring target molecule of an MSH5 protein, in an amount sufficient to modulate MSH5 expression or MSH5 activity, thereby preventing fertilization in a subject.  
     
     
         11 . The method of  claim 10 , wherein said compound is capable of modulating MSH5 expression.  
     
     
         12 . The method of  claim 10 , wherein said compound is capable of modulating MSH5 activity.  
     
     
         13 . The method of  claim 10 , wherein said MSH5 activity is modulation of ovarian meiosis.  
     
     
         14 . The method of  claim 10 , wherein said MSH5 activity is modulation of chromosome pairing.  
     
     
         15 . The method of  claim 10 , wherein said MSH5 activity is modulation of chromosome synapsis.  
     
     
         16 . The method of  claim 10 , wherein said compound comprises the nucleic acid molecule shown in  FIG. 1A  or a fragment thereof.  
     
     
         17 . A method for modulating meiosis in a subject comprising administering to a subject a compound selected from the group consisting of an MSH5 peptide, an MSH5 nucleic acid molecule, an antisense MSH5 nucleic acid molecule, an anti-MSH5 antibody, and a naturally-occurring target molecule of an MSH5 protein, in an amount sufficient to modulate MSH5 expression or MSH5 activity, thereby modulating meiosis in a subject.  
     
     
         18 . The method of  claim 17 , wherein said compound comprises the nucleic acid molecule shown in  FIG. 1A  or a fragment thereof.  
     
     
         19 . A method for modulating MSH5 expression or MSH5 activity in a subject comprising administering to a subject a compound selected from the group consisting of an MSH5 peptide, an MSH5 nucleic acid molecule, an antisense MSH5 nucleic acid molecule, an anti-MSH5 antibody, and a naturally-occurring target molecule of an MSH5 protein, in an amount sufficient to modulate MSH5 expression or MSH5 activity, thereby moduling MSH5 expression or MSH5 activity in a subject.  
     
     
         20 . The method of  claim 19 , wherein said compound comprises the nucleic acid molecule shown in  FIG. 1A  or a fragment thereof.