Because MeCP2 expression and its binding was increased with prenatal ethanol exposure, we hypothesized that MeCP2 is involved in regulating POMC expression. To test this hypothesis we knocked down MeCP2 expression using shRNA specific to MeCP2 by delivering a lentivirus (10 million pfu) into the third ventricle of AF, AD and PF rat offspring. The results show that MeCP2 expression in the MBH was significantly reduced following MeCP2 shRNA treatment compared to scrshRNA treatment in AD, PF and AF rat offspring (Fig. 4A). Determination of POMC expression in MBH samples of scr shRNA and MeCP2 shRNA treated rats revealed that MeCP2 shRNA treatment increased POMC mRNA expression in AF but not in AD and PF rats (Fig. 4B). Additionally, POMC mRNA levels in MeCP2 shRNA-treated AF rats were comparable to those of scr shRNA and MeCP2 shRNA treated AD and PF rats. These results suggest that MeCP2 plays an important role in fetal alcohol-induced suppression of POMC gene.
