Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes

Molecular Autism
Monica SonzogniYpe Elgersma


Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutations affecting UBE3A gene expression. Previous studies in mice revealed distinct critical periods during neurodevelopment in which reactivation of Ube3a gene expression can prevent the onset of behavioral deficits. Whether UBE3A is required for brain function throughout life is unknown. Here, we address the importance of maintaining UBE3A expression after normal brain development. Using a conditional mouse, we deleted the Ube3a gene at three ages spanning brain maturation. We assessed the consequences of Ube3a gene deletion by testing the mice in behavioral tasks previously shown to produce robust phenotypes in AS model mice. Early embryonic deletion of Ube3a recapitulated all behavioral deficits of AS mice. In contrast, Ube3a gene deletion at 3 or 12 weeks of age did not have a significant effect on most behavioral tasks and did not increase seizure sensitivity. Taken together, these results emphasize that UBE3A critically impacts early brain development, but plays a more limited role in adulthood. Our findings provide important considerations for upcoming clinical trials in which UBE3A gene expression is reactivated and suggest that even transient U...Continue Reading


Sep 7, 2019·Autism Research : Official Journal of the International Society for Autism Research·Mark J Zylka
Aug 21, 2020·Learning & Memory·Maria N Schultz, Jacqueline N Crawley


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Related Concepts

Brain Diseases
Gene Deletion
Neurodevelopmental Disorders
UBE3A gene
Gene Expression
Angelman Syndrome
Brain Function
Clinical Trials

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Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.