Although it is well established that deletion of SNORD116 contributes to PWS in humans, mice missing Snord116 don’t display hyperphagia and obesity. This makes it very difficult to study the biology of SNORD116 and test anti-obesity drugs. In a major breakthrough, Dr. Yeo’s group has shown that if Snord116 is deleted in adult mice, a percentage of them do display the hallmark PWS features of obesity and hyperphagia. Studying this novel model in detail will help us understand SNORD116 function and also provide a new model for testing therapeutic interventions for obesity and hyperphagia in PWS.
ABSTRACT: The role of the brain in controlling food intake is increasingly apparent, with studies finding that genes related to obesity often play a role in brain regions crucial for feeding, appetite, and satiety. Prader-Willi syndrome, one of the most common forms of genetic obesity, results increased food intake (hyperphagia) leading to severe obesity, as well mental retardation, infertility, and short stature. Prader-Willi Syndrome is known to be caused by deletions on human chromosome 15, which has been recently narrowed down to encompass of a cluster of non-coding RNAs called SNORD116. Whenever studying the brain, animal models are required, very often mice, because we clearly cannot get into the brain of a living human. The problem with mouse models of PWS to date however, including those in which Snord116 have been deleted, is they don’t display hyperphagia and obesity. In fact, they are actually born smaller and remain smaller than normal mice all through life. In a major breakthrough, we have shown that if you delete Snord116 in mice as an adult, then the mice do display the hallmark PWS features of obesity and hyperphagia. However, currently, this only happens to some of the mice. Here, we are interested in studying this model in detail, and to find out why only some of the mice become obese. This novel PWS mouse model with hyperphagia and obesity will open up significant new avenues for identifying the underlying pathophysiology of PWS. Furthermore, this model would serve as a unique platform for testing the efficacy of interventions aiming to prevent or reverse obesity and hyperphagia in PWS. We thus hope to provide new insights into how deficiency of Snord116 affects the brain control of food intake, and provide the PWS research community with new models to investigate the hallmark phenotypes of obesity and hyperphagia associated with PWS.