In P2RX5 knockout mice the anti-obesity effect of CL316,243 was vastly reduced, and limited to a decrease in body weight gain (F(2,218) = 8.90, p = 0.0002) and increased fat free mass gain (F(2,14) = 4.09, p = 0.04, while ATPγS (2 mg/Kg) was completely ineffective (Figure 4b–e,f–i; Supplementary Figure S3e). This evidence concerns the gene P2RX5 and obesity due to melanocortin 4 receptor deficiency.