T-Bet Compositions and Methods of Use Thereof

Abstract

Isolated nucleic acid molecules encoding T-bet, and isolated T-bet polypeptides, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a T-bet transgene. The invention further provides T-bet fusion proteins and anti-T-bet antibodies. Methods of using the T-bet compositions of the invention are also disclosed, including methods for detecting T-bet expression and/or activity in a biological sample, methods of modulating T-bet expression and/or activity in a cell, and methods for identifying agents that modulate the expression and/or activity of T-bet.

1 - 55 . (canceled) 
     
     
         56 . A nonhuman transgenic animal that contains cells carrying a transgene encoding a T-bet polypeptide. 
     
     
         57 . The transgenic animal of  claim 56 , wherein the non-human animal is a mouse. 
     
     
         58 . A nonhuman animal comprising in its genome an exogenous DNA molecule that functionally disrupts a T-bet gene of the non-human animal, wherein the animal exhibits a phenotype characterized by decreased IFN-γ production, relative to a wild-type animal. 
     
     
         59 . The transgenic animal of  claim 58 , wherein the non-human animal is a mouse. 
     
     
         60 . A recombinant cell comprising an exogenous T-bet molecule or a portion thereof, and a reporter gene operably linked to a regulatory region responsive to T-bet such that upon activation of T-bet, transcription of the reporter gene occurs. 
     
     
         61 - 115 . (canceled) 
     
     
         116 . A method for modulating T-bet expression and/or activity in a cell comprising contacting the cell with an agent that modulates T-bet expression and/or activity such that T-bet expression and/or activity in the cell is modulated. 
     
     
         117 . The method of  claim 116 , wherein the agent increases the activity of T-bet. 
     
     
         118 . The method of  claim 116 , wherein the agent decreases the activity of T-bet. 
     
     
         119 . The method of  claim 116 , wherein the agent increases the expression of T-bet. 
     
     
         120 . The method of  claim 116 , wherein the agent decreases the expression of T-bet. 
     
     
         121 - 172 . (canceled) 
     
     
         173 . A method of treating or preventing a disorder that would benefit from treatment with an agent that modulates the expression and/or activity of T-bet comprising administering to a subject with said disorder an agent that modulates the expression and/or activity of T-bet. 
     
     
         174 . (canceled) 
     
     
         175 . The method of  claim 173 , wherein the disorder is an autoimmune disease. 
     
     
         176 - 181 . (canceled) 
     
     
         182 . The method of  claim 173 , wherein the disorder is asthma. 
     
     
         183 - 188 . (canceled) 
     
     
         189 . A method for identifying a compound that modulates the expression and/or activity of a T-bet polypeptide, comprising
 providing an indicator composition that comprises a T-bet polypeptide;   contacting the indicator composition with a test compound; and   determining the effect of the test compound on the expression and/or activity of the T-bet polypeptide in the indicator composition to thereby identify a compound that modulates the expression and/or activity of a T-bet polypeptide.   
     
     
         190 . The method of  claim 189 , wherein:
 the indicator composition comprises a T-bet polypeptide and a DNA molecule to which the T-bet polypeptide binds; and   the effect of the test compound on the expression and/or activity of the T-bet polypeptide is determined by evaluating the binding of the T-bet polypeptide to the DNA molecule in the presence and absence of the test compound.   
     
     
         191 - 208 . (canceled) 
     
     
         209 . A method of identifying a compound that modulates a signal transduction pathway involving T-bet comprising:
 a) contacting cells deficient in T-bet with a test compound; and   b) determining the effect of the test compound on an expression and/or activity of T-bet, the test compound being identified as a modulator of the expression and/or activity of a signal transduction pathway involving T-bet based on the ability of the test compound to modulate a signal transduction pathway involving T-bet in the cells deficient in T-bet.   
     
     
         210 . The method of  claim 209 , wherein the cells deficient in T-bet are in a non-human T-bet deficient animal and the cells are contacted with the test compound by administering the test compound to the non-human T-bet deficient animal. 
     
     
         211 - 256 . (canceled)