Alleles of the human mu opioid receptor, diagnostic methods using said alleles, and methods of treatment based thereon

Abstract

Provided herein are variant alleles of a gene encoding a mu opioid receptor, along with cloning vectors for replicating such variant alleles, expressing vectors for expressing the variant alleles to produce variant mu opioid receptors, and antibodies to such variant receptors. Also disclosed are binding characteristics of such variant receptors regarding binding to opioid ligands, and the using of such binding characteristics to diagnose a subjects susceptibility to pain, susceptibility to an addictive disease, selecting an appropriate pain reliever along with a therapeutically effective amount of the reliever to administer to a subject suffering from pain. In addition, diagnostic methods for diagnosing a disease or disorder such as infertility, constipation, diarrhea, decreased immune response relative to a standard, and decreased ability to withstand stress relative to a standard, along with commercial kits for diagnosing such diseases or disorders. Furthermore, the invention is also directed to identification of targeted prevention methods, early therapeutic intervention, and improved treatment of opioid addiction, infertility, constipation, diarrhea, impaired immune responsiveness, and stress.

1 - 141 . (canceled)  
     
     
         142 . An isolated variant human mu opioid receptor comprising an amino acid sequence having one or more of the following variations in SEQ ID NO:2: 
 a) the serine at position 23 of SEQ ID NO:2 is replaced with a proline;    b) the serine at position 42 of SEQ ID NO:2 is replaced with a threonine;    c) the addition of a glycine residue following the glycine at position 63.    
     
     
         143 . An antibody having a variant human mu opioid receptor of  claim 142  as an immunogen.  
     
     
         144 . The antibody of  claim 143 , detectably labeled.  
     
     
         145 . An isolated variant human mu opioid receptor comprising an amino acid sequence having at least two variations in SEQ ID NO:2, wherein at least one of said variations comprises one of the following: 
 a) the serine at position 23 of SEQ ID NO:2 is replaced with a proline;    b) the serine at position 42 of SEQ ID NO:2 is replaced with a threonine;    c) the addition of a glycine residue following the glycine at position 63.    
     
     
         146 . An antibody having a variant human mu opioid receptor of  claim 145  as an immunogen.  
     
     
         147 . The antibody of  claim 146 , detectably labeled.  
     
     
         148 . A commercial test kit for detecting a variant human mu opioid receptor in a bodily sample taken from a subject, comprising: 
 (a) a predetermined amount of at least one detectably labeled immunochemically reactive component having affinity for a variant human mu opioid receptor, wherein said variant human mu opioid receptor comprises an amino acid sequence having one or more of the following variations in SEQ ID NO:2: 
 i) the serine at position 23 of SEQ ID NO:2 is replaced with a proline;  
 ii) the serine at position 42 of SEQ ID NO:2 is replaced with a threonine;  
 iii) the addition of a glycine residue following the glycine at position 63;  
   (b) other reagents; and    (c) directions for use of the kit.    
     
     
         149 . A commercial test kit for detecting a variant human mu opioid receptor in a bodily sample taken from a subject, wherein said variant human mu opioid receptor comprises an amino acid sequence having one or more of the following variations in SEQ ID NO:2: 
 a) the serine at position 23 of SEQ ID NO:2 is replaced with a proline;    b) the serine at position 42 of SEQ ID NO:2 is replaced with a threonine;    c) the addition of a glycine residue following the glycine at position 63, wherein said kit comprises:    d) a labeled component which has been obtained by coupling the variant human mu opioid receptor of the bodily sample to a detectable label;    e) one or more additional immunochemical reagents of which at least one reagent is a ligand or an immobilized ligand, which ligand comprises: 
 (i) a ligand capable of binding with the labeled component d);  
 (ii) a ligand capable of binding with a binding partner of the labeled component d);  
 (iii) a ligand capable of binding with at least one of the component(s) to be determined; or  
 (iv) a ligand capable of binding with at least one of the binding partners of at least one of the component(s) to be determined;  
   f) directions for the performance of a protocol for the detection and/or determination of one or more components of an immunochemical reaction between the human mu opioid receptor and a specific binding partner thereto.