Pancreas-specific proteins

Abstract

The present invention discloses polynucleotides which identify and encode DP119, DP444, DP810, DP685, WE474, DP160, RA977, or RA770 as well as novel functions for these proteins of the inventions. The invention provides for compositions for disorders associated with the expression of the proteins of the invention, such as for the treatment, alleviation and/or prevention of pancreatic dysfunction (for example diabetes, hyperglycemia, and impaired glucose tolerance), and related disorders, and other disease and disorders.

1 . Use of a nucleic acid molecule selected from DP119, DP444, DP810, DF685, WE474, DP160, RA977, or RA770 or a polypeptide encoded thereby or a fragment or variant of said nucleic acid molecule or said polypeptide or an effector/modulator of said nucleic acid or said polypeptide for the manufacture of a pharmaceutical agent.  
     
     
         2 . The use of  claim 1  wherein the nucleic acid molecule is a vertebrate nucleic acid, particularly a human nucleic acid, or a fragment thereof or variant thereof.  
     
     
         3 . The use of  claim 1 , wherein said nucleic acid molecule 
 (a) hybridizes under stringent conditions to the nucleic acid molecule of SEQ ID NO: 1, 3, 5, 7, 9, 11, 12, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43 and/or the complementary strand thereof,    (b) it is degenerate with respect to the nucleic acid molecule of (a),    (c) encodes a polypeptide which is at least 80% identical to SEQ ID NO:2, 4, 6, 8, 10, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44 or    (d) differs from the nucleic acid molecule of (a) to (c) by mutation and wherein said mutation causes an alteration, deletion, duplication or premature stop in the encoded polypeptide.    
     
     
         4 . The use of  claim 1 , wherein the nucleic acid molecule is a DNA molecule.  
     
     
         5 . The use of  claim 1 , wherein the nucleic acid molecule encodes a protein of the invention specifically expressed in pancreatic tissues or other tissues.  
     
     
         6 . The use of  claim 1 , wherein said nucleic acid molecule is a recombinant nucleic acid molecule.  
     
     
         7 . The use of  claim 6 , wherein said recombinant nucleic acid molecule is a vector, particularly an expression vector.  
     
     
         8 . The use of  claim 1 , wherein said polypeptide is a recombinant polypeptide.  
     
     
         9 . The use of  claim 8 , wherein said polypeptide is a fusion polypeptide.  
     
     
         10 . The use of  claim 1 , wherein said nucleic acid molecule is selected from hybridization probes, primers and anti-sense oligonucleotides and aptamers.  
     
     
         11 . The use of  claim 1  for diagnostic applications.  
     
     
         12 . The use of  claim 1  for therapeutic applications.  
     
     
         13 . The use of  claim 1  for the manufacture of an agent for diagnosis, monitoring, prevention or treatment of pancreatic disorders, such as diabetes and related disorders, as well as neurodegenerative disorders, and other diseases.  
     
     
         14 . The use of  claim 13  for detecting and/or verifying, for the treatment, alleviation and/or prevention of a pancreatic dysfunction (for example diabetes, hyperglycemia, and impaired glucose tolerance), and related disorders including obesity, and neurodegenerative disorders, and others, in cells, cell masses, organs and/or subjects.  
     
     
         15 . The use of  claim 13  for promoting the differentiation and/or function of beta-cells in vitro and/or in vivo.  
     
     
         16 . The use of  claim 13  for the regeneration of beta-cells in vitro and/or in vivo.  
     
     
         17 . Use of a nucleic acid molecule selected from DP119, DP444, DP810, DP685, WE474, DPI 60, RA977, or RA770 or a polypeptide encoded thereby or a fragment or variant of said nucleic acid molecule or said polypeptide or an effector/modulator of said nucleic acid molecule or said polypeptide as defined in  claim 1  for monitoring and/or controlling the function of a gene and/or a gene product which is influenced and/or modified by a DP119, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide.  
     
     
         18 . Use of a nucleic acid molecule selected from DP119, DP444, DP810, DP685, WE474, or RA977 or a polypeptide encoded thereby or a fragment or variant of said nucleic acid molecule or said polypeptide or an effector/modulator of said nucleic acid molecule or said polypeptide as defined in  claim 1  for identifying substances capable of interacting with a DP119, DP444, DP810, DP685, WE474, DP160, RA977, or RA770 polypeptide.  
     
     
         19 . A non-human transgenic animal exhibiting a modified expression of a DP119, DP444, DP810, DP685, WE474, DP160, RA977, or RA770 polypeptide.  
     
     
         20 . The animal of  claim 19 , wherein the expression of DP119, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide is increased and/or reduced.  
     
     
         21 . A recombinant host cell exhibiting a modified expression of a DP119, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide.  
     
     
         22 . The cell of  claim 21  which is a human cell.  
     
     
         23 . A method of identifying a (poly)peptide involved in a metabolic disorder or metabolic syndrome, particularly in pancreatic dysfunction, in a mammal comprising the steps of 
 (a) contacting a collection of test (poly)peptides with a DP119, DP444, DP810, DP685, WE474, DP160, RA977, or RA770 polypeptide or a fragment thereof under conditions that allow binding of said test (poly)peptide;    (b) removing test (poly)peptides which do not bind and    (c) identifying test (poly)peptides that bind to said DP119, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide or the fragment thereof.    
     
     
         24 . A method of screening for an agent which modulates the interaction of a DP1 19, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide or a fragment thereof with a binding target/agent, comprising the steps of 
 (a) incubating a mixture comprising 
 (aa) a DP119, DP444, DP810, DP685, WE474, DP160, RA977, or 
 RA770 polypeptide or a fragment thereof;  
 
 (ab) a binding target/agent of said DP119, DP444, DP81 0, DP685, 
 WE474, DP160, RA977, or RA770 polypeptide or fragment thereof; and  
 
 (ac) a candidate agent 
 under conditions whereby said DP119, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide or fragment thereof specifically binds to said binding target/agent at a reference affinity;  
 
   (b) detecting the binding affinity of said DP119, DP444, DP810, DP685, WE474, DP160, RA977, or RA770 polypeptide or fragment thereof to said binding target to determine an (candidate) agent-biased affinity; and    (c) determining a difference between (candidate) agent-biased affinity and the reference affinity.    
     
     
         25 . A method of screening for an agent which modulates the activity of a DP119, DP444, DP810, DP685, WE474, DP160, RA977, or 25 RA770 polypeptide, comprising the steps of 
 (a) incubating a mixture comprising 
 (aa) a DP119, DP444, DP81 0, DP685, WE474, DP160, RA977, or RA770 polypeptide or a fragment thereof; and 
 (ab) a candidate agent  
 
   b) a vector comprising the nucleic acid of (a);    (c) a host cell comprising the nucleic acid molecule of (a) or the    
     
     
         26 . A method of producing a composition comprising mixing a (poly)peptide identified by the method of  claim 23  with a pharmaceutically acceptable carrier and/or diluent.  
     
     
         27 . The method of  claim 26  wherein said composition is a pharmaceutical composition is a pharmaceutical composition for preventing, alleviating or treating of a pancreatic dysfunction (for example diabetes, hyperglycemia, and impaired glucose tolerance), and related disorders including obesity, and neurodegenerative disorders, and others.  
     
     
         28 . Use of a (poly)peptide as identified by the method of  claim 23  for the preparation of a pharmaceutical composition for the treatment, alleviation and/or prevention of a pancreatic dysfunction (for example diabetes, hyperglycemia, and impaired glucose tolerance), and related disorders including obesity, and neurodegenerative disorders, and others.  
     
     
         29 . Use of a nucleic acid molecule of the DP119, DP444, DP810, DP685, WE474, DP160, RA977 or RA770 gene family or of a fragment thereof for the preparation of a non-human animal which over- or underexpresses the DP119, DP444, DP810, DP685, WE474, DP160, RA977, RA770 gene product.  
     
     
         30 . Kit comprising of at least one of 
 (a) a DP119, DP444, DP810, DP685, WE474, DP160, RA977, or RA770 nucleic acid molecule or a fragment thereof;    (b) a vector comprising the nucleic acid of (a);    (c) a host cell comprising the nucleic acid molecule of (a) or the vector of (b);    (d) a polypeptide encoded by the nucleic acid molecule of (a);    (e) a fusion polypeptide encoded by the nucleic acid molecule of (a);    (f) an antibody, an aptamer or another receptor the nucleic acid molecule of (a) or the polypeptide of (d) or (e) and    (g) an anti-sense oligonucleotide of the nucleic acid molecule of (a).    
     
     
         31 . A method of producing a composition comprising mixing an agent identified by the method of  claim 24  with a pharmaceutically acceptable carrier and/or diluent.  
     
     
         32 . Use of an agent as identified by the method of  claim 24  for the preparation of a pharmaceutical composition for the treatment, alleviation and/or prevention of a pancreatic dysfunction (for example diabetes, hyperglycemia, and impaired glucose tolerance), and related disorders including obesity, and neurodegenerative disorders, and others.