Genome‐wide association studies (GWAS) have revealed that human AC3 (hAC3) is associated with obesity.[19, 20, 21, 22, 23, 24, 25, 26, 27] To examine the function of human AC3 (hAC3) in regulating body weight, we generated a humanized mouse by introducing the complete hAC3 sequence into the Rosa26 site in the mouse genome (Figure S1, Supporting Information). Here, ADCY3 is linked to obesity due to melanocortin 4 receptor deficiency.