Analysis of tissue-specific and PPARα-dependent induction of FABP gene expression in the mouse liver by an in vivo DNA electroporation method

Peroxisome proliferator (PPAR)α ligand Wy14,643 induces liver-fatty acid binding protein (FABP) spontaneously and heart-FABP gradually, but not intestine-FABP mRNA expression in the mouse liver. These strict regulations have not been reproduced in cultured cell systems. We applied a DNA electroporation method to directly introduce reporter gene constructs into the livers of mice. This system reproduced the in vivo responses of the above three FABP gene promoters to the PPARα ligand but not that of a promoter containing the typical three PPAR binding sites in tandem. Deletion and mutation analyses of the mouse L-FABP gene suggested that, in addition to the binding site for PPARα, a far upstream sequence is required for PPAR-dependent transactivation in the liver. In contrast to the cultured cell systems, our in vivo DNA electroporation method showed that PPARα binding to the promoter is necessary but not sufficient for PPARα ligand-dependent transcriptional activation of the L-FABP gene in vivo.