Orphan nuclear receptor

Abstract

The present invention relates to a novel human orphan nuclear receptor that binds to a cytochrome P-450 monooxygenase (CYP) promoter and that is activated by compounds that induce CYP gene expression. The invention further relates to nucleic acid sequences encoding such a receptor, to methods of making the receptor and to methods of using the receptor and nucleic acid sequences encoding same. The invention also relates to non-human animals transformed to express the human receptor and to methods of using such animals to screen compounds for drug interactions and toxicities.

1 . An isolated human nuclear receptor that binds to a cytochrome P-450 monooxygenase promoter, or a DNA binding or ligand binding domain thereof. 
     
     
         2 . The receptor according to  claim 1  wherein the promoter is a cytochrome P-450 monooxygenase 3A4 (CYP3A4) promoter. 
     
     
         3 . The receptor according to  claim 2  wherein said receptor is hPXR. 
     
     
         4 . An isolated human nuclear receptor having the amino acid sequence given  FIG. 1 , or a fragment thereof, of at least 30 consecutive amino acids. 
     
     
         5 . A fusion protein comprising a DNA binding or ligand binding domain of hPXR and a non-hPXR-derived sequence. 
     
     
         6 . An isolated nucleic acid comprising a sequence encoding the receptor of  claim 1 . 
     
     
         7 . A construct comprising the nucleic acid of  claim 6  and a vector. 
     
     
         8 . A host cell comprising the construct of  claim 7 . 
     
     
         9 . A method of making the receptor of  claim 3 , or fragment thereof, comprising:
 culturing a host cell containing an expression construct comprising a sequence encoding said receptor, or fragment thereof, operably linked to a promoter, under conditions such that said receptor, or fragment thereof, is produced, and   isolating said receptor, or fragment thereof.