Taken as a whole, these data show that the insertion of either WT- or R165W-hMC4R in the mouse MC4R locus led to 2 obesity models that recapitulated several of the characteristics observed in obese patients with MC4R deficit, albeit with a modestly lower penetrance for the WT human allele. This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.