OCT 2017 – Hypothalamus Specific Re‐Introduction of SNORD116 Increased Energy Expenditure
The Snord116 gene cluster has been recognised as a critical contributor to PWS, with mice lacking Snord116 displaying many classical PWS characteristics, including low postnatal body weight, reduced bone mass and increased food intake. However, these mice do not develop obesity due to increased energy expenditure. To understand the physiological function of Snord116 better and potentially rescue the altered metabolism of Snord116 deficient mice, researchers used an adeno-associated viral (AAV) approach to reintroduce the Snord116 gene product into the hypothalamus in Snord116 deficient mice at different ages.
Results showed that mid-hypothalamic re-introduction of Snord116 in 6-week old Snord116 deficient mice leads to significantly reduced body weight and weight gain, associated with elevated energy expenditure. Importantly, when the intervention targets other areas such as the anterior region of the hypothalamus or the reintroduction occurs in older mice the positive effects on energy expenditure are diminished. These data indicated that the metabolic symptoms of PWS develop gradually and the Snord116 gene plays a critical role during this process. Furthermore, when they investigated the consequences of Snord116 re-introduction under conditions of thermo-neutrality where the mild cold stress influences are avoided, they also observed a significant increase in energy expenditure.
They concluded that the rescue of mid-hypothalamic Snord116 deficiency in young Snord116 germline deletion mice increases energy expenditure, providing fundamental information contributing to potential virus-mediated genetic therapy in PWS. Click to read more about Snord116 research studies at the Garvan Institute.