Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels is not well understood. Mouse Cftr mRNA shows strain-dependent expression differences that cannot be fully explained by variation at non-Cftr loci. Differences in tracheal and colonic expression appear to be due predominantly to elements linked to Cftr. Fifteen single nucleotide sequence variations were found within 1.4 kb 5 0 to the translation start site between the inbred lines A/J, C57BL/6J and 129/SvJ. In

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... ddition, 129/SvJ carries a 100 bp deletion relative to the other two strains. These variants were investigated by sequentially deleting 5 0 regions and measuring luciferase reporter activity from transfected, mouse epithelial cell lines derived from pancreatic duct, renal collecting duct, salivary gland and trachea. These assays identified a region between 2524 and 2834 in the C57BL/6J promoter, but not in A/J or 129/SvJ, capable of repressing expression. Sequence analysis and gel mobility shift assays suggest that the transcription factor MZF is involved in the strain-dependent effect. It was also apparent that several reporter constructs displayed expression differences between cell lines, possibly indicating the presence of tissue-specific elements.