Myers Luke S, Christian Sarah G, Simpson Sean, Sper Renan, Taylor Clint, Montes Laura, Jepp Thomas B C, Ramos Daniela, Schuller Livia, Konganti Kranti, Friedeck Wade, Habib Ozair, Hodge McKaela, Taylor Alasdair J, Coffell Ashley, Schlafer Annalise, Matt Morgan, Revell Bradley, Knight Carol, Barreña Cristina C, Murphy William J, Weeber Edwin J, Segal David J, Anderson Anne, Nash Kevin R, Silverman Jill L, Piedrahita Jorge A, Dindot Scott V
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843.
Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford GU2 7YH, United Kingdom.
Proc Natl Acad Sci U S A. 2025 Jul 29;122(30):e2505152122. doi: 10.1073/pnas.2505152122. Epub 2025 Jul 21.
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 () 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 () with a maternally inherited deletion of () have altered postnatal behaviors, impaired vocalizations, reduced brain growth, motor incoordination, and ataxia. Neonatal 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.
安吉尔曼综合征是一种神经发育障碍，其特征为严重的运动和认知缺陷。它是由印记泛素蛋白连接酶E3A（UBE3A）基因的母系遗传等位基因缺失所致。安吉尔曼综合征的啮齿动物模型不能完全重现与该病症相关的所有症状，并且作为治疗开发的临床前模型存在局限性。在此，我们表明，母系遗传缺失UBE3A的猪表现出产后行为改变、发声受损、脑生长减缓、运动不协调和共济失调。新生的UBE3A缺失猪表现出在患有安吉尔曼综合征的婴儿中观察到的几种症状，包括肌张力减退、哺乳缺陷和生长发育不良。总体而言，这些发现与在安吉尔曼综合征患者中观察到的病理生理学和发育轨迹一致。我们预计，这种猪模型将增进我们对安吉尔曼综合征病理生理学的理解，并用作治疗开发的临床前大型动物模型。
