Elevated gastrin secretion by in vivo gene electroporation in skeletal muscle

Whether or not in vivo gene transfer of gastrin gene into skeletal muscle by electroporation could modify gastrin secretion was examined. The expression plasmid vector, either pMEPrGaspA encoding the rat gastrin gene or pEGFP-N1 encoding the GFP reporter gene was injected into M. rectus abdominis of rats or M. biceps formis of mice. Subsequently, square electric pulses of direct current were applied six times at 25 V with a loading period of 100 msec per pulse. Clear foreign gene expression in the skeletal muscle was demonstrated by both GFP fluorescence and immunostaining of rat gastrin. Time course changes in plasma gastrin levels after transfection revealed that in rats, gastrin gene transfer significantly increased the plasma gastrin level for 4 weeks post-transfection (P<0.05), but the difference diminished at the end of the 10-week period. In mice, plasma gastrin level elevated similarly for 3 weeks, and pH of gastric contents decreased in the gastrin gene transfected group compared with the control counterpart (P<0.05). These findings suggest that localized in vivo gene transfer by electroporation allows skeletal muscle to become an artificial endocrine tissue for hormonal manipulation of animals.