Gene and protein specific for excitable tissues

Abstract

The present invention relates to OTB182, and all facets of novel polynucleotides encoded by it, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are expressed in excitable tissues, such as heart, brain, and muscle, and are therefore useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, such neuropathy, neuralgic amyotrophy (e.g., HNA), myopathy, sensorineural hearing loss (e.g., DFNA20), mental retardation, neuromuscular disorders, and other diseases especially relating to excitable tissues, such as heart, brain, and muscle.

1 . An isolated polynucleotide comprising, a polynucleotide sequence coding without interruption for a human OTB182 polypeptide, or a complement thereto, 
 said OTB182 having 95% or more amino acid sequence identity along its entire length to SEQ ID NO 2.    
     
     
         2 . An isolated polynucleotide of  claim 1 , which codes for human OTB182 as set forth in SEQ ID NO 2.  
     
     
         3 . An isolated polynucleotide of  claim 1 , which is SEQ ID NO 1.  
     
     
         4 . An isolated polynucleotide comprising a polynucleotide sequence coding for a human OTB182 polypeptide having 95% or more amino acid sequence identity along its entire length to the sequence coding for amino acids 123-307 of SEQ ID NO 2, or a fragment thereof, which polynucleotide is specific for said human OTB182.  
     
     
         5 . An isolated polynucleotide of  claim 4 , wherein said fragment is effective in a polymerase chain reaction.  
     
     
         6 . An isolated polynucleotide of  claim 4  consisting essentially of a polynucleotide sequence coding for amino acids 123-307 of SEQ ID NO 2, or a polynucleotide fragment thereof.  
     
     
         7 . An isolated human OTB182 polypeptide having an amino acid sequence of  claim 1 .  
     
     
         8 . An isolated human OTB182 polypeptide having an amino acid sequence of  claim 2 .  
     
     
         9 . An isolated human OTB182 polypeptide having an amino acid sequence of  claim 4 .  
     
     
         10 . An isolated human OTB182 polypeptide having an amino acid sequence of  claim 6 , or a fragment thereof which is specific for a human OTB182.  
     
     
         11 . A method of detecting expression of a gene coding for human OTB182, comprising, 
 contacting a sample comprising nucleic acid with a polynucleotide probe specific for a human OTB182 of  claim 1  under conditions effective for said probe to hybridize specifically with said human OTB182, and    detecting hybridization between said probe and said human OTB182.    
     
     
         12 . A method of  claim 11 , wherein said detecting is performed by: 
 Northern blot analysis, polymerase chain reaction (PCR), reverse transcriptase PCR, RACE PCR, or in situ hybridization.    
     
     
         13 . A method for identifying an agent that modulates the expression of a human OTB182 gene, or the biological activity of polypeptide encoded thereby, in cells expressing said gene, comprising, 
 contacting cells expressing human OTB182 of  claim 1  with a test agent under conditions effective for said test agent to modulate the expression of a gene coding for said human OTB182, or the biological activity of a polypeptide encoded thereby, and    determining whether said test agent modulates said human OTB182.    
     
     
         14 . A method of  claim 13 , wherein said agent is an antisense polynucleotide which is effective to inhibit translation of said human OTB182.  
     
     
         15 . A method of detecting polymorphisms in human OTB182 comprising: 
 comparing the structure of: genomic DNA comprising all or part of human OTB182, mRNA comprising all or part of human OTB182, cDNA comprising all or part of human OTB182, or a polypeptide comprising all or part of human OTB182, with the complete structure of human OTB182 as set forth in SEQ ID NO 1.    
     
     
         16 . A method of  claim 15 , wherein said polymorphism is a nucleotide deletion, substitution, inversion, or transposition.  
     
     
         17 . A method of  claim 15 , wherein said polymorphism is a mutation associated with hereditary neuralgic amyotrophy.  
     
     
         18 . A mammalian cell whose genome comprises a functional disruption of the human OTB182 gene of  claim 1 .  
     
     
         19 . A non-human, transgenic mammal comprising a cell of  claim 18 , which has a defect in an excitable cell.  
     
     
         20 . An antibody which is specific-for: 
 an epitope selected from amino acids 123-307 of SEQ ID NO 2, or comprising amino acid 27, 47, 64, 66, 75, 78, 105, 111, or 113 of SEQ ID NO 2.    
     
     
         21 . A method of selecting a human OTB182 polynucleotide or amino acid sequence from a database, comprising: 
 displaying, in a computer-readable medium, a polynucleotide sequence or polypeptide sequence for human OTB182 of  claim 1 , or complements to the polynucleotides sequence, wherein said displayed sequences have been retrieved from said database upon selection by a user.