Mice carrying the WT allele of the human MC4R (WT-hMC4R) in place of the mouse MC4R (mMC4R) gene developed a “hypomorphic” phenotype leading to obesity because of a lower sensitivity of the human receptor to α–melanocyte-stimulating hormone (α-MSH) as compared with the mouse receptor. Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.