A remarkable decrease in hypothalamic oxytocin (Oxt) and PVN melanocortin 4 receptor (Mc4r) mRNA was also demonstrated in conditional Sim1 homozygous and germ line Sim1 heterozygous mutant mice suggesting that hyperphagic obesity may be attributable to changes in the leptin-melanocortin-oxytocin pathway [105]. This evidence concerns the gene SIM1 and obesity due to melanocortin 4 receptor deficiency.