Elevated delta power in a maternal UBE3A-deletion pig model of Angelman syndrome.

BACKGROUND

Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternally inherited UBE3A allele and characterized by severe cognitive, motor, and communication impairments. Increased delta (1-4 Hz) activity on electroencephalogram (EEG) is a well-established biomarker of Angelman syndrome in humans and rodent models and is increasingly used as a quantitative outcome measure in therapeutic studies. Whether this electrophysiological phenotype is present in the recently developed pig model has not been evaluated.

METHODS

Scalp EEG recordings were obtained from freely moving Yorkshire-Landrace pigs carrying a maternal UBE3A deletion (UBE3A-/+) and wild-type littermates across three developmental age groups. Artifact-free EEG epochs were identified, behavioral states were classified using synchronized video, and relative delta power was quantified using spectral analysis.

RESULTS

UBE3A-/+ pigs showed higher relative delta power than wild-type pigs during both awake and asleep vigilance states, with the largest genotype differences observed during wakefulness. Across development, UBE3A-/+ pigs also showed a smaller increase in delta power during the transition from the awake to the asleep state compared with wild-type pigs.

CONCLUSIONS

These findings demonstrate that the maternal UBE3A-deletion pig model reproduces the elevated delta power EEG phenotype characteristic of Angelman syndrome. Noninvasive scalp EEG therefore represents a translationally relevant approach for assessing neural dysfunction and therapeutic responses in this large-animal model.