Elevated Delta Power in a Maternal UBE3A -Deletion Pig Model of Angelman Syndrome

Abstract Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternally inherited UBE3A allele and is characterized by severe cognitive, motor, and communication impairments. Increased delta (1– 4 Hz) activity on electroencephalogram (EEG) assessed by visual inspection and by spectral power analysis is a robust feature of the disorder in humans and rodent models and is used as a biomarker of Angelman syndrome. This aspect of the phenotype has not been evaluated in the recently developed pig model of Angelman syndrome. Here, we analyzed scalp EEG recordings from freely moving pigs carrying a maternal UBE3A deletion (UBE3A-/+) across three age groups to determine whether they recapitulate the delta power abnormalities characteristic of the disorder. UBE3A-/+ pigs exhibited elevated delta power during both wakefulness and sleep compared with wild-type littermates, with the largest differences observed during the awake state. The typical increase in delta power that accompanies the transition from wakefulness to sleep was also reduced in UBE3A-/+ pigs. These effects were observed across study groups, demonstrating that the maternal UBE3A-deletion pig model reproduces the elevated delta power EEG phenotype of Angelman syndrome. Our results establish noninvasive scalp EEG as a translationally relevant tool for assessing neural dysfunction in this large-animal model and provide a framework for preclinical therapeutic testing. This work strengthens the utility of the pig model for mechanistic studies and therapeutic development in Angelman syndrome. Competing Interest Statement SVD has an equity interest and is an employee at Ultragenyx Pharmaceutical