Biology subjects

Christian, S. G.

Publications and source records attributed to Christian, S. G..

3 recordsLinked to original sources

bioRxiv2026

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

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.

neuroscience↗

bioRxiv2025

MRI-Based Quantification of Central Nervous System Tissue and Cerebrospinal Fluid Volumes in Developing Pigs

There is a growing need for alternative animal models to test brain-targeted therapies, and pigs are emerging as a promising option. Their utility, however, depends on reliable estimations of central nervous system (CNS) tissue and cerebrospinal fluid (CSF) volumes, which are essential for translating therapeutic doses between studies in animals and humans. To address this need, we conducted a cross-sectional study of 12 commercial pigs (Sus scrofa) across four age groups (2, 5, 11, and 19 weeks). High-resolution magnetic resonance images (MRI) of the brain and spinal cord were acquired using T2-weighted turbo spin echo with fat saturation and short tau inversion recovery scans. CNS tissue and CSF volumes were segmented and quantified using 3D Slicer, along with additional anatomical measurements. Our findings reveal notable age-related changes, including spinal CSF volume surpassing brain CSF volume in older pigs, highlighting shifts in CSF distribution that may influence dosing and delivery strategies for CNS-targeted therapies. This study provides a reference for future research using pig models in CNS disease studies and underscores the importance of incorporating brain and spinal CSF and CNS volume data into preclinical models.

neuroscience↗

bioRxiv2025

A preclinical pig model of Angelman syndrome mirrors the early developmental trajectory of the human condition

Angelman syndrome is a neurodevelopmental disorder characterized by severe motor and cognitive deficits. It is caused by the loss of the maternally inherited allele of the imprinted ubiquitin-protein ligase E3A (UBE3A) gene. Rodent models of Angelman syndrome do not fully recapitulate all the symptoms associated with the condition and are limited as a preclinical model for therapeutic development. Here, we show that pigs (Sus scrofa) with a maternally inherited deletion of UBE3A (UBE3A-/+) have altered postnatal behaviors, impaired vocalizations, reduced brain growth, motor incoordination, and ataxia. Neonatal UBE3A-/+ pigs exhibited several symptoms observed in infants with Angelman syndrome, including hypotonia, suckling deficits, and failure to thrive. Collectively, these findings are consistent with the pathophysiology and developmental trajectory observed in individuals with Angelman syndrome. We anticipate that this pig model will advance our understanding of the pathophysiology of Angelman syndrome and be used as a preclinical large animal model for therapeutic development.

genetics↗