Sleep is a significant challenge in both SYS and PWS. This project, led by Dr. Andrew Liu, will use a new mouse model of Schaaf-Yang syndrome (SYS) to investigate how the protein MAGEL2 regulates normal sleep and other cyclic behaviors.
This project investigates how changes in the MAGEL2 gene disrupt normal sleep and daily circadian rhythms in both Prader–Willi (PWS) and Schaaf–Yang (SYS) syndromes. Both conditions share core clinical features, including sleep problems and daytime sleepiness, which greatly affect the quality of life for both patients and caregivers. Because MAGEL2 is central to both disorders, understanding its role in sleep is key to uncovering and developing targeted treatments that benefit individuals with PWS and SYS. Scientists already know that MAGEL2 helps regulate the brain’s internal clock, but how gene changes cause sleep disruption remains unclear. Our team found that cells made from the dental pulp of SYS and PWS patients show defects in their internal circadian timing system, suggesting that MAGEL2 plays a vital role in controlling sleep–wake cycles. Now we have created the first mouse carrying the same MAGEL2 mutation found in humans with SYS. This is a major step forward. While cell studies are essential, they capture only part of the picture. Mouse models will help us to understand how MAGEL2 changes affect the entire body, brain, and behavior, including the sleep–wake cycle. We will study these mice with advanced tools that record biological rhythms, mobility, and sleep. Our new mouse model provides a powerful foundation for future research, extending to other symptoms of the disorder and enabling drug discovery. As a living system for testing and developing new therapies, it will help bridge the gap between laboratory findings and clinical treatments, moving us closer to effective interventions that restore healthy sleep and improve quality of life for individuals with PWS and SYS.