Hyperphagia and obesity are the best-known manifestations of Prader-Willi syndrome (PWS) and are responsible for most of the overall morbidity and mortality associated with the disease. Yet these PWS symptoms remain poorly understood and without effective pharmacologic therapies. Mouse models attempting to recapitulate both the genetic alterations and marked hyperphagia plus obesity of PWS have been enigmatic, leading to skepticism about the use of mouse models to investigate PWS. In this issue of the JCI, Polex-Wolf and colleagues challenge the skeptics by successfully inducing hyperphagia following bilateral mediobasal hypothalamic deletion of the Snord116 gene from adult mice. Obesity also resulted, although only in a subset of mice. While this approach represents an exciting advance, highlighting a pathologic effect of loss of mediobasal hypothalamic Snord116 expression on the development of PWS’s hallmark symptoms, the variability in the body-weight and body composition responses to this site-selective gene deletion raises several questions.

食欲亢进和肥胖是Prader-Willi综合征（PWS）的最著名表现，并且是与该疾病有关的大多数总体发病率和死亡率的原因。然而，这些PWS症状仍知之甚少，并且没有有效的药物治疗方法。试图概括PWS的遗传变异和明显的食欲亢进和肥胖的小鼠模型一直是个谜，这引起了人们对使用小鼠模型研究PWS的怀疑。在本期JCI中，Polex-Wolf及其同事通过从成年小鼠的双侧中下丘脑缺失Snord116基因成功诱导食欲亢进，向怀疑论者发起挑战。肥胖也导致了，尽管仅在一部分小鼠中。虽然这种方法代表了令人兴奋的进步，