Article
Neurosciences
James J. Fink, Jeremy D. Schreiner, Judy E. Bloom, Jadin James, Dylan S. Baker, Tiwanna M. Robinson, Richard Lieberman, Leslie M. Loew, Stormy J. Chamberlain, Eric S. Levine
Summary: The study investigated electrophysiological phenotypes in induced pluripotent stem cell-derived neurons from patients with Dup15q, revealing several potential mechanisms of neuronal hyperexcitability and seizure susceptibility. These findings may offer new targets for the treatment of seizures and other associated phenotypes in Dup15q.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Elizabeth L. Berg, Shekib A. Jami, Stela P. Petkova, Annuska Berz, Timothy A. Fenton, Jason P. Lerch, David J. Segal, John A. Gray, Jacob Ellegood, Markus Woehr, Jill L. Silverman
Summary: Angelman syndrome is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor deficits, impaired communication, and happy demeanor; researchers discovered excessive laughter-like ultrasonic emissions in a rat model of AS, suggesting an excitable, playful personality similar to individuals with AS. The unique phenotypes of this rat model, including aberrant social interactions and cognitive impairments, provide advantages for evaluating therapies for AS compared to available mouse models.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Lei Xing, Jeremy M. Simon, Travis S. Ptacek, Jason J. Yi, Lipin Loo, Hanqian Mao, Justin M. Wolter, Eric S. McCoy, Smita R. Paranjape, Bonnie Taylor-Blake, Mark J. Zylka
Summary: The Ube3a gene mutation can cause neurodevelopmental disorders regardless of parent of origin. A mouse model with the autism-linked UBE3AT485A gain-of-function mutation was created. Both paternal and maternal expression of UBE3AT503A led to increased UBE3A activity in neural progenitors and glial cells. Maternal expression of UBE3AT503A also resulted in elevated UBE3A activity in neurons, but not paternal expression. The phenotypes of mutant mice differed depending on the parent of origin.
Article
Genetics & Heredity
N. A. Copping, J. L. Silverman
Summary: Our study focused on translational neurophysiological outcomes in an Angelman Syndrome (AS) model. We found that Ube3a-del mice have a reduced seizure threshold and increased epileptiform spiking activity and delta power in EEG compared to WT. Additionally, Ube3a-del mice show less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages, and fewer sleep spindles, which are critical for memory consolidation.
Article
Multidisciplinary Sciences
Dilara Sen, Zuzana Drobna, Albert J. Keung
Summary: This study evaluated the specificities of seven commercial UBE3A antibodies and found that three of them showed substantial nonspecific immunoreactivity. While four antibodies demonstrated specific localization patterns in both mouse brain sections and human cerebral organoids, they varied significantly in background signals and staining patterns in undifferentiated human pluripotent stem cells.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Ana Moreira-de-Sa, Francisco Q. Goncalves, Joao P. Lopes, Henrique B. Silva, Angelo R. Tome, Rodrigo A. Cunha, Paula M. Canas
Summary: Research suggests that administration of A(2A) receptor antagonists can improve motor deficits in an Angelman syndrome mouse model and correct synaptic alterations in the cerebellum and striatum.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Genetics & Heredity
Meimiao Fang, Yali Li, Jin Ren, Ronggui Hu, Xiaobo Gao, Liang Chen
Summary: The study revealed a novel role for UBE3A in regulating downstream genes of the retinoic acid signaling pathway, potentially shedding light on a drug target for Angelman syndrome.
FRONTIERS IN GENETICS
(2021)
Article
Behavioral Sciences
Andie Dodge, Jonathan Willman, Matthew Willman, Austin W. Nenninger, Nicole K. Morrill, Kristina Lamens, Hayden Greene, Edwin J. Weeber, Kevin R. Nash
Summary: Angelman syndrome is a rare genetic disorder caused by disruptions to the maternally inherited allele UBE3A. The disorder presents severe and lifelong symptoms, including intractable seizures, abnormal EEG's, ataxic gait, lack of speech, and a notably happy demeanor. Research on the neurophysiological underpinnings of UBE3A in Angelman Syndrome is ongoing to elucidate potential therapeutic targets.
Article
Cell Biology
Linn Amanda Syding, Agnieszka Kubik-Zahorodna, Petr Nickl, Vendula Novosadova, Jana Kopkanova, Petr Kasparek, Jan Prochazka, Radislav Sedlacek
Summary: A novel mouse model with a complete deletion of the Ube3a gene exhibits important phenotypes characteristic of Angelman syndrome, including motor dysfunction and behavioral abnormalities.
Article
Cell & Tissue Engineering
Marwa Elamin, Aurelie Dumarchey, Christopher Stoddard, Tiwanna M. Robinson, Christopher Cowie, Dea Gorka, Stormy J. Chamberlain, Eric S. Levine
Summary: Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder characterized by autism and epilepsy. UBE3A, an imprinted gene expressed only from the maternal allele, is believed to be a major driver of Dup15q. In this study, Dup15q neurons showed increased excitability compared to control neurons, and normalizing UBE3A levels using antisense oligonucleotides prevented this phenotype. However, UBE3A overexpression resulted in a similar profile to Dup15q neurons, suggesting the involvement of other genes in the duplicated region.
Article
Biochemistry & Molecular Biology
Chao-Wen Lin, Yi-Chun Cheng, Chang-Hao Yang, Hsien-Sung Huang
Summary: This study found that extended exposure to white or blue light can promote the expression of the Angelman syndrome-related gene UBE3A in the retina but not in the visual cortex. Additionally, it was observed that this light exposure caused changes in the chromatin structure of the Ube3a promoter, which further impacted gene expression.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
A. Mattijs Punt, Matthew C. Judson, Michael S. Sidorov, Brittany N. Williams, Naomi S. Johnson, Sabine Belder, Dion den Hertog, Courtney R. Davis, Maximillian S. Feygin, Patrick F. Lang, Mehrnoush Aghadavoud Jolfaei, Patrick J. Curran, Wilfred F. J. van Ijcken, Ype Elgersma, Benjamin D. Philpot
Summary: Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. While overexpression of the UBE3A gene is presumed to be the main cause of Dup15q pathology, studies on mouse models with UBE3A overexpression have yielded conflicting results. In this study, transgenic mouse models were used to investigate the neurodevelopmental impact of Ube3a gene overdosage and found limited effects on neurodevelopment, but increased mortality when faced with seizures.
Article
Nanoscience & Nanotechnology
R. Mezzena, C. Masciullo, S. Antonini, F. Cremisi, M. Scheffner, M. Cecchini, I Tonazzini
Summary: During neuronal development, focal adhesions play a key role in integrating external signals and promoting neuronal pathfinding and migration. The ubiquitin ligase UBE3A has a crucial function in the nervous system, and changes in its expression levels can lead to neurodevelopmental disorders. Studies using nano/micro-structured anisotropic substrates have shown deficits in contact guidance in cells with UBE3A deficiency.
Article
Multidisciplinary Sciences
Jacinta I. Kalisch-Smith, Nikita Ved, Dorota Szumska, Jacob Munro, Michael Troup, Shelley E. Harris, Helena Rodriguez-Caro, Aimee Jacquemot, Jack J. Miller, Eleanor M. Stuart, Magda Wolna, Emily Hardman, Fabrice Prin, Eva Lana-Elola, Rifdat Aoidi, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Timothy J. Mohun, Samira Lakhal-Littleton, Sarah De Val, Eleni Giannoulatou, Duncan B. Sparrow
Summary: Congenital heart disease is a common human birth defect with many cases potentially caused by maternal iron deficiency, which can be prevented by iron administration in early pregnancy. Genetic predisposition and environmental factors may interact to impact the development of heart disease.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Xiaonan Du, Ji Wang, Shuang Li, Yu Ma, Tianqi Wang, Bingbing Wu, Yuanfeng Zhou, Lifei Yu, Yi Wang
Summary: This study assessed the phenotype and genotype of Chinese children with Angelman syndrome and found that the majority of patients had maternal deletions and an expanded mutation spectrum for UBE3A variants. Patients in the deletion group had earlier diagnosis, more severe clinical phenotype, and higher rates of epilepsy with multiple seizure types and medication use.