Compositions for the diagnosis and treatment of chediak-higashi syndrome

Abstract

The present invention relates to the identification of novel nucleic acid molecules and proteins encoded by such nucleic acid molecules or degenerate variants thereof, that participate in the differentiation and/or function of intracellular vesicles. The nucleic acid molecules of the present invention represent the genes corresponding to the mammalian bg gene, a gene that, when mutated, is responsible for the human Chediak-Higashi syndrome.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule containing the nucleotide sequence of FIG. 4 (SEQ ID NO:1), FIG. 7 or FIG. 8.  
     
     
         2 . An isolated nucleic acid molecule capable of complementing a bg mutation, having a nucleotide sequence that: 
 (a) encodes the amino acid sequence shown in FIG. 4, FIG. 7 or FIG. 8; or    (b) hybridizes under stringent conditions to the nucleotide sequence of (a) or to its complement.    
     
     
         3 . A nucleotide vector containing the nucleotide sequence of  claim 1  or  2 .  
     
     
         4 . An expression vector containing the nucleotide sequence of  claim 1  or  2  in operative association with a nucleotide regulatory sequence that controls expression of the nucleotide sequence in a host cell.  
     
     
         5 . The expression vector of  claim 4 , wherein said regulatory element is selected from the group consisting of the cytomegalovirus hCMV immediate early gene, the early or late promoters of SV40 adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage A, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase, the promoters of acid phosphatase, and the promoters of the yeast α-mating factors.  
     
     
         6 . A genetically engineered host cell that contains the nucleotide sequence of  claim 1  or  2 .  
     
     
         7 . A genetically engineered host cell that contains the nucleotide sequence of  claim 1  or  2  in operative association with a nucleotide regulatory sequence that controls expression of the nucleotide sequence in the host cell.  
     
     
         8 . An isolated bg protein.  
     
     
         9 . The isolated bg protein of  claim 8 , wherein the protein has the amino acid sequence shown in FIG. 4, FIG. 7 or FIG. 8.  
     
     
         10 . An antibody that immunospecifically binds the bg protein of  claim 8 .  
     
     
         11 . A method for diagnosing intracellular vesicle disorders, in a mammal, comprising measuring bg gene expression in a patient sample.  
     
     
         12 . The method of  claim 11  in which expression is measured by detecting mRNA transcripts of the bg gene.  
     
     
         13 . The method of  claim 11  in which expression is measured by detecting the bg gene product.  
     
     
         14 . A method for diagnosing intracellular vesicle disorders in a mammal, comprising detecting a bg gene mutation contained in the genome of the mammal.  
     
     
         15 . The method of  claim 14  in which the mutation is located in a splice site of the bg gene.  
     
     
         16 . The method of  claim 11  or  14  wherein the intracellular vesicle disorder is Chediak-Higashi syndrome.  
     
     
         17 . A method for screening compounds useful for the treatment of intracellular vesicle disorders, comprising contacting a compound with a cultured cell that expresses the bg gene, and detecting a change in the expression of the bg gene by the cultured cell.  
     
     
         18 . The method of  claim 17  wherein the intracellular vesicle disorder is Chediak-Higashi syndrome.  
     
     
         19 . A method for treating an intracellular vesicle disorder, in a mammal comprising administering a compound to the mammal that modulates the expression of the bg gene in the mammal.  
     
     
         20 . The method of  claim 19  in which the intracel lular vesicle disorder is Chediak-Higashi syndrome.