Ange gene in atopy

Abstract

The present invention relates to isolated nucleic acid sequences of ANGE, CLLD8 and CLLD7 or sequences complementary or substantially homologous thereto or fragments thereof. Also provided are sequences comprising hybrid nucleic acid sequences from two or more of the genes. Also provided are nucleic acid expression vectors, polypeptides, antibodies to the polypeptides, host cells, non-human transgenic animals and pharmaceutical compositions and agents. Also provided is the use of the nucleic acid sequence and/or protein in medicine and research, methods for diagnosing or determining predisposition to disease or severity of disease, methods for preventing or treating disease, and kits for use in the methods and the use of the nucleic acid sequence and protein in treating or preventing IgE mediated diseases and non-atopic asthma, and in screens for identifying new agents for use in the methods.

1 - 86 . (canceled) 
     
     
         87 . A method for identifying an agent for treating an IgE mediated disease which modulates the activity of a CLLD8-ANGE hybrid polypeptide or a splice variant thereof comprising:
 providing an CLLD8-ANGE hybrid polypeptide or splice variant thereof   providing a substrate;   providing an agent to be tested;   measuring whether the agent to be tested modulates the activity of the polypeptide by   measuring processing of the substrate.   
     
     
         88 . A method for identifying an agent for treating an IgE mediated disease which modulates the activity of an ANGE or CLLD8-ANGE hybrid polypeptide or the activity of any splice variant thereof comprising:
 providing an ANGE or CLLD8-ANGE hybrid polypeptide or splice variant thereof;   providing an agent to be tested;   providing a cell;   measuring a change in differentiation or proliferation of the cell.   
     
     
         89 . A method according to  claim 88 , wherein the change is a change in phenotype. 
     
     
         90 . A method according to  claim 88 , where the cell is expressing a polypeptide encoded by an isolated or recombinant nucleic acid molecule comprising an ANGE or a CLLD8-ANGE hybrid mRNA sequence or splice variant thereof. 
     
     
         91 . A method according to  claim 88  where the change in cellular differentiation involves a change in expression of a cell signalling factor. 
     
     
         92 . A method according to  claim 88 , wherein the cell is a B-lymphocyte. 
     
     
         93 . A method according to  claim 91 , wherein the cell signalling factor is an immunomodulator or a peptide regulatory factor. 
     
     
         94 . A method according to  claim 88 , wherein the cell is cultured following removal from a patient or experimental animal. 
     
     
         95 . A method for identifying an agent for treating an IgE mediated disease which modulates the activity of ANGE or CLLD8-ANGE hybrid or any splice variant thereof comprising:
 providing a transgenic animal comprising a vector comprising an isolated or recombinant nucleic acid molecule comprising an ANGE or a CLLD8-ANGE hybrid mRNA sequence or splice variant thereof which results in disease;   providing an agent to be tested;   contacting the transgenic animal with the agent to be tested;   detecting a change in the transgenic animals phenotype.   
     
     
         96 . A method for detecting a side effect associated with the use of an anti IgE-mediated disease agent which modulates the activity of an ANGE or ANGE-CLLD8 hybrid polypeptide or any splice variant thereof comprising:
 providing a cell which does not substantially express an ANGE or CLLD8-ANGE hybrid polypeptide or a splice variant thereof;   providing an agent to be tested;   contacting the agent to be tested with the cell; and   measuring any side effect produced by the agent on the cell.   
     
     
         97 . A method according to  claim 96  where the side effect involves a change in cell differentiation. 
     
     
         98 . A method according to  claim 96  where the side effect involves a change in cell proliferation. 
     
     
         99 . A method according to  claim 96  where the cell is part of a transgenic animal. 
     
     
         100 . A method according to  claim 96  where the side effect is a measure of a change of phenotype. 
     
     
         101 . A method for identifying an agent for treating an IgE mediated disease which modulates the activity of ANGE or CLLD8-ANGE hybrid or any splice variant thereof comprising:
 providing an isolated nucleic acid sequence encoding ANGE or CLLD8-ANGE hybrid or a splice variant of either;   providing an agent to be tested;   measuring whether the agent to be tested modulates the activity of the isolated nucleic acid by measuring the interaction of the agent with the sample of nucleic acid.   
     
     
         102 . A method according to  claim 101  where the screen is an in vitro transcription assay measuring transcription of ANGE or CLLD8-ANGE hybrid or of any splice variant thereof. 
     
     
         103 . A method for identifying an agent for treating an IgE mediated disease which modulates the activity of ANGE or CLLD8-ANGE hybrid or any splice variant thereof comprising:
 providing a cell producing nucleic acid encoding an ANGE or CLLD8-ANGE hybrid polypeptide or a splice variant of either;   providing an agent to be tested;   measuring whether the agent to be tested modulates the activity of said nucleic acid by measuring the interaction of the agent with said nucleic acid produced by said cell.   
     
     
         104 . A method for identifying an agent for treating an IgE mediated disease wherein said method comprises:
 providing an ANGE or CLLD8-ANGE polypeptide or a splice variant thereof;   providing an agent to be tested; and   measuring whether the agent to be tested modulates the activity of said ANGE or CLLD8-ANGE polypeptide or a splice variant thereof.   
     
     
         105 . A method according to  claim 104  wherein the activity that is measured is activity of a methyl-CpG-binding domain or a SET domain of ANGE-CLLD8 polypeptide or a splice variant thereof. 
     
     
         106 . A method according to  claim 104  wherein the activity that is measured is histone methyl transferase activity of a SET domain of ANGE-CLLD8 polypeptide or a splice variant thereo 
     
     
         107 . A method according to  claim 104  wherein the activity that is measured is activity of a PHD domain of an ANGE or ANGE-CLLD8 polypeptide or a splice variant thereof. 
     
     
         108 . A method for identifying an agent for treating an IgE mediated disease wherein said method comprises:
 providing a cell producing an ANGE or CLLD8-ANGE polypeptide or a splice variant of either,   providing an agent to be tested; and   measuring whether the agent to be tested modulates the activity of said ANGE or CLLD8-ANGE polypeptide or a splice variant thereof produced by said cell.   
     
     
         109 . A method according to  claim 108  wherein the activity that is measured is activity of a methyl-CpG-binding domain, a SET domain of ANGE-CLLD8 polypeptide or a splice variant thereof. 
     
     
         110 . A method according to  claim 108  wherein the activity that is measured is histone methyl transferase activity of a SET domain of ANGE-CLLD8 polypeptide or a splice variant thereof. 
     
     
         111 . A method according to  claim 108  wherein the activity that is measured is activity of a PHD domain of an ANGE or ANGE-CLLD8 polypeptide or a splice variant thereof. 
     
     
         112 . A method according to  claim 87  wherein said polypeptide comprises the sequence set forth in SEQ IDS NO:27. 
     
     
         113 . A method according to  claim 87  wherein said polypeptide comprises the sequence set forth in SEQ IDS NO:27. 
     
     
         114 . A method according to  claim 108  wherein said polypeptide comprises the sequence set forth in SEQ IDS NO:27. 
     
     
         115 . A method according to  claim 87  wherein said IgE mediated disease is asthma, atopy, hayfever, eczema, atopic dermatitis or allergic rhinitis. 
     
     
         116 . A method according to  claim 104  wherein said IgE mediated disease is asthma, atopy, hayfever, eczema, atopic dermatitis or allergic rhinitis. 
     
     
         117 . A method according to  claim 108  wherein said IgE mediated disease is asthma, atopy, hayfever, eczema, atopic dermatitis or allergic rhinitis.