The ob/ob mouse, with a single point mutation at codon 105 in the leptin gene (Zhang et al., 1994), is totally leptin deficient, and presents with a phenotype including severe hyperphasia, a low basal metabolic rate, and rapid onset obesity (Pelleymounter et al., 1995), now known to result from over-expression of hypothalamic NPY and MCH, and low expression of POMC (Ahima and Osy, 2004). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.