7B2 Knockout transgenic animals as models of endocrine disease

Abstract

In general, the invention features methods and uses for transposon-mediated gene targeting which greatly enhance the insertion and detection of desired genes in genomic exons by homologous recombination. The invention also features transgenic non-human mammals, and eukaryotic cells, wherein a gene encoding 7B2 protein is modified, as well as nucleic acid vectors capable of undergoing homologous recombination with an endogenous 7B2 gene in a cell. The invention also features transgenic non-human mammals as models of endocrine disorders, as well as methods for diagnosing and treating patients with endocrine disorders.

1 . A transgenic non-human mammal, wherein a gene encoding 7B2 protein is modified, whereby 7B2 protein activity is reduced. 
   
   
       2 - 13 . (canceled) 
   
   
       14 . A nucleic acid vector comprising nucleic acid capable of undergoing homologous recombination with an endogenous 7B2 gene in a cell, wherein said homologous recombination results in a modification of the 7B2 gene resulting in decreased 7B2 protein activity in the cell. 
   
   
       15 . (canceled) 
   
   
       16 . A eukaryotic cell, wherein the endogenous gene encoding 7B2 protein is modified, resulting in reduced 7B2 protein activity in the cell. 
   
   
       17 - 18 . (canceled) 
   
   
       19 . A eukaryotic cell containing an endogenous 7B2 gene into which there is integrated a transposon comprising DNA encoding a selectable marker. 
   
   
       20 . A method for diagnosing a mammal for an endocrine disorder, said method comprising determining whether 7B2 protein activity is abnormal in said mammal, whereby said abnormal activity indicates that said mammal has an endocrine disorder or an increased likelihood of developing an endocrine disorder. 
   
   
       21 - 34 . (canceled) 
   
   
       35 . A method for determining whether a compound is potentially useful for treating or alleviating the symptoms of an endocrine disorder, said method comprising:
 (a) providing a cell comprising a reporter gene operably linked to the promoter from a 7B2 gene;   (b) contacting said cell with said compound; and   (c) measuring the expression of said reporter gene;   
     whereby a change in the level of said expression in response to said compound indicates that the compound is potentially useful for treating or alleviating the symptoms of an endocrine disorder. 
   
   
       36 . A method for determining whether a compound is potentially useful for treating or alleviating the symptoms of an endocrine disorder, said method comprising:
 (a) providing a cell that produces a 7B2 protein;   (b) contacting said cell with said compound; and   (c) monitoring the activity of said 7B2 protein;   
     whereby a change in activity in response to said compound indicates that the compound is potentially useful for treating or alleviating the symptoms of an endocrine disorder. 
   
   
       37 - 47 . (canceled)