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Expression of CFTR from a ciliated cell-specific promoter is ineffective at correcting nasal potential difference in CF mice
The expression of human CFTR (cystic fibrosis transmembrane conductance regulator) in the ciliated cells of the nasal epithelia in cystic fibrosis mice fails to significantly change their nasal bioelectrics.
If gene therapy is successful, a sufficient amount of the gene in question is expressed in the right cell type(s). To improve gene transfer specificity for cystic fibrosis and other airway diseases, scientists from the University of North Carolina (USA) developed cell-type specific promoters to ensure that transgenes will be expressed in the correct airway cell types.
The team used a FOXJ1 promoter construct to generate a transgenic mouse model expressing human CFTR in their tracheal and nasal epithelia. The level of CFTR expression was greater or equal to the expressed murine CFTR and immunoprecipitation and western blotting demonstrated the production of human CFTR protein. Immunohistochemistry confirmed that CFTR was expressed in the apical region of ciliated cells.
The transgenic mice were bred to CFTR null mice to find out, if the expression of CFTR from the FOXJ1 promoter can compensate for the airway defects accompanied by cystric fibrosis like Cl- secretion and Na+ absorption. But the expression of human CFTR failed to cure the effects of the disease.
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26.03.2008 | Anna Lena Marwedel 
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