Psychology

UBE3A

Gene

Neurology

Neuroscience

Bioinformatics

Biology

Phenotype

Angelman syndrome

Genetics

Medicine

Ubiquitin ligase

Psychiatry

Ubiquitin

Molecular Autism

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 ...

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