P2Y4 Receptor transgenic and knockout non-human mammals

Abstract

This invention provides a receptor having a preference for pyrimidine nucleotides preferably uridine triphosphate over purine nucleotides. A receptor having a preference for pyrimidine nucleotides over purine nucleotides means a receptor for which pyrimidine nucleotides and purine nucleotides are not equally active and equipotent. This means that the receptor according to the invention in presence of these agonists presents a functional response (preferably the accumulation of Inositol triphosphate (IP3), diacylglycerol (DAG), or calcium ions) to lower concentration of pyrimidine nucleotides, preferably uridine triphosphate, than to purine nucleotides or a more important functional response to similar concentration of pyrimidine nucleotide than to purine nucleotide

1 . A transgenic non human mammal whose genome comprises a nucleic acid construct comprising a DNA sequence encoding a receptor which binds nucleotides, wherein said receptor comprises the amino acid sequence of SEQ ID NO:2.  
     
     
         2 . The transgenic non human mammal of  claim 1 , wherein said mammal expresses said receptor.  
     
     
         3 . The transgenic non human mammal of  claim 2 , wherein said mammal over expresses said receptor.  
     
     
         4 . The transgenic non human mammal of  claim 2 , wherein said mammal expresses said receptor ectopically.  
     
     
         5 . The transgenic non human mammal of  claim 1 , wherein said DNA sequence encoding a receptor is a genomic DNA sequence.  
     
     
         6 . The transgenic non human mammal of  claim 1 , wherein said DNA sequence encoding a receptor is a cDNA sequence.  
     
     
         7 . The transgenic non human mammal of  claim 6 , wherein said cDNA sequence comprises SEQ ID NO:1.  
     
     
         8 . The transgenic non human mammal of  claim 1 , whose genome comprises more than one copy of said nucleic acid construct comprising said DNA sequence encoding said receptor.  
     
     
         9 . The transgenic non human mammal of  claim 1 , wherein the mammal is a mouse.  
     
     
         10 . The transgenic non human mammal of  claim 1 , wherein said construct comprises an inducible promoter operably linked to a DNA sequence encoding a receptor which binds nucleotides, wherein said receptor comprises the amino acid sequence shown in SEQ ID NO:2.  
     
     
         11 . The transgenic non human mammal of  claim 10 , wherein said construct additionally comprises tissue specific regulatory elements.