Transgenic GPCR expressing animals

Abstract

The invention provides isolated nucleic acids molecules, designated muscarinic acetylcholine receptor 6 (“mACHR-6”) nucleic acid molecules, which encode polypeptides involved in the modulation of acetylcholine responses in acetylcholine responsive cells. The invention also provides antisense nucleic acid molecules, expression vectors containing mACHR-6 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which an mACHR-6 gene has been introduced or disrupted. The invention still further provides isolated mACHR-6 polypeptides, fusion polypeptides, antigenic peptides, and anti-mACHR-6 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

1 . A non-human transgenic animal, which expresses an mACHR-6 polypeptide or a biologically active portion thereof.  
     
     
         2 . The transgenic animal of  claim 1 , wherein said mACHR-6 polypeptide is a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5 or 32.  
     
     
         3 . The transgenic animal of  claim 1 , wherein said animal exhibits a central nervous system disorder.  
     
     
         4 . The transgenic animal of  claim 1 , wherein said animal exhibits a disorder selected from the group consisting of a cognitive disorder and an eating disorder.  
     
     
         5 . A non-human transgenic animal containing a transgene comprising the nucleotide sequence of SEQ ID NO:1, 4, or 31, or a fragment thereof.  
     
     
         6 . The transgenic animal of  claim 5 , wherein the transgene comprises intronic sequences or polyadenylation signals.  
     
     
         7 . The transgenic animal of  claim 5 , wherein the transgene is operably linked to a tissue-specific regulatory sequence.  
     
     
         8 . The transgenic animal of  claim 5 , wherein said animal exhibits a cognitive disorder.  
     
     
         9 . The transgenic animal of  claim 8 , wherein said cognitive disorder is selected from the group consisting of a memory disorder, a learning disorder, a learning disability, and Alzheimer's related memory loss.  
     
     
         10 . The transgenic animal of  claim 5 , wherein said animal exhibits an eating disorder.  
     
     
         11 . The transgenic animal of  claim 5 , wherein said animal is homozygous or heterozygous for said transgene.  
     
     
         12 . The transgenic animal of  claim 5 , wherein said animal is a mouse.  
     
     
         13 . An isolated cell, or a purified preparation of cells from the transgenic animal of  claim 5 .  
     
     
         14 . A homologous recombinant mouse in which the gene encoding the GPCR mACHR-6 is overexpressed.  
     
     
         15 . The homologous recombinant mouse of  claim 14 , wherein said mouse exhibits an eating disorder.  
     
     
         16 . The homologous recombinant mouse of  claim 14 , wherein said mouse exhibits a cognitive disorder.  
     
     
         17 . The homologous recombinant mouse of  claim 16 , wherein said cognitive disorder is selected from the group consisting of a memory disorder, a learning disorder, a learning disability, and Alzheimer's related memory loss.  
     
     
         18 . An isolated cell, or a purified preparation of cells from the homologous recombinant mouse of  claim 14 .  
     
     
         19 . The isolated cell of  claim 18 , wherein the cell is selected from the group consisting of a brain cell, a gland cell and a smooth muscle cell.  
     
     
         20 . The isolated cell of  claim 18 , wherein the cell is a neurotransmitter responsive cell.