A preclinical pig model of Angelman syndrome mirrors the early developmental trajectory of the human condition
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (28)
Luke S. Myers
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Sarah G. Christian
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Sean Simpson
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University
Renan Sper
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University
Clint Taylor
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Laura Montes
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Thomas B. C. Jepp
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Daniela Ramos
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Livia Schuller
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Kranti Konganti
Texas A&M University Institute for Genome Sciences and Society, Texas A&M University
Wade Friedeck
Veterinary Medical Teaching Hospital, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Ozair Habib
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
McKaela Hodge
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Alasdair J. Taylor
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Ashley Coffell
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Annalise Schlafer
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Morgan Matt
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Bradley Revell
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Carol Knight
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
Cristina Cardona-Barreña
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
William J. Murphy
Edwin J. Weeber
Department of Molecular Pharmacology and Physiology, University of South Florida
David J. Segal
MIND Institute, University of California Davis School of Medicine
Anne Anderson
Department of Pediatrics, Baylor College of Medicine
Kevin R. Nash
Department of Molecular Pharmacology and Physiology, University of South Florida
Jill L. Silverman
MIND Institute, University of California Davis School of Medicine
Jorge A. Piedrahita
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University
Scott V. Dindot
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University