Since reduced SOCS3 expression in the Arc would tend to increase signaling by leptin and other cytokines to promote leanness, the regulation of hypothalamic SOCS3 expression by STAT5 is also unlikely to underlie the obesity of the Stat5fl/fl; Nestin-Cre mice. The gene discussed is SOCS3; the disease is obesity due to melanocortin 4 receptor deficiency.