Angelman syndrome is a rare (~1:15,000) neurodevelopmental disorder characterized by severe developmental delay and intellectual disability, impaired communication skills and motor deficits. Angelman syndrome is caused by the loss of the maternally inherited allele of the ubiquitin-protein ligase E3A (UBE3A) gene. While rodent models of Angelman syndrome such as Ube3a maternal deficiency mice are available, they present limitations that decrease their translational value. A study in PNAS reports the development of a genetically modified pig (Sus scrofa) model with complete deletion of the UBE3A gene using CRISPR/Cas9 and somatic cell nuclear transfer technologies. Using a breeding strategy to produce pigs with a maternal- or paternal-derived deletion of UBE3A, the researchers demonstrated that pigs with a deletion of the maternal — but not paternal — UBE3A allele showed alterations in postnatal behaviors, impaired vocalizations, reduced brain growth, motor incoordination and ataxia. This new pig model, which exhibit several symptoms observed in infants with Angelman syndrome, will be useful to further understand the pathophysiology of Angelman syndrome and identify potential therapies.
Original reference: Myers, L. S. et al. Proc. Natl Acad. Sci. USA 122, e2505152122 (2025)
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