Funding outcome

Children with the genetic disorder Prader-Willi syndrome have neonatal feeding difficulties, developmental delay, and endocrine dysfunction. They develop excess fat tissue in childhood, and in the absence of strict intervention, they typically develop life-threatening obesity. Prader-Willi syndrome occurs in about 1:15,000 births and is caused by the deletion of part of a chromosome containing a group of genes. One of these genes is called MAGEL2. MAGEL2 is important for recycling or destroying worn-out proteins in the brain. MAGEL2 does this by assisting other proteins, called ubiquitin ligases. MAGEL2 is important in the brain cells that sense how much fat the body has. The brain does this by measuring how much leptin, a hormone made by fat cells, is in the bloodstream. The brain receptor that senses leptin is normally recycled for reuse within the cell. We think that MAGEL2 is important for recycling of the leptin receptor in the brain. We will test whether MAGEL2 interacts with a specific ubiquitin ligase that is involved in leptin receptor recycling. We think that without MAGEL2, children with Prader-Willi do not properly recycle their worn-out leptin receptors. In this case, their brain cells may not realize that they already have enough fat and enough leptin, so the children become obese. We find out how MAGEL2 fits into the network of proteins and processes that are critical for the development of obesity in young children. Lastly, this study will also help us to understand the genes and protein that are involved in many other types of early onset childhood obesity