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

Background: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutations affecting gene expression. Previous studies in mice revealed distinct critical periods during neurodevelopment in which reactivation of gene expression can prevent the onset of behavioral deficits. Whether UBE3A is required for brain function throughout life is unknown.

A behavioral test battery for mouse models of Angelman syndrome: a powerful tool for testing drugs and novel mutants.

Background: Angelman syndrome (AS) is a neurodevelopmental disorder caused by mutations affecting UBE3A function. AS is characterized by intellectual disability, impaired motor coordination, epilepsy, and behavioral abnormalities including autism spectrum disorder features. The development of treatments for AS heavily relies on the ability to test the efficacy of drugs in mouse models that show reliable, and preferably clinically relevant, phenotypes.

Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model.

Angelman syndrome (AS) is a severe neurodevelopmental disorder that results from loss of function of the maternal ubiquitin protein ligase E3A (UBE3A) allele. Due to neuron-specific imprinting, the paternal UBE3A copy is silenced. Previous studies in murine models have demonstrated that strategies to activate the paternal Ube3a allele are feasible; however, a recent study showed that pharmacological Ube3a gene reactivation in adulthood failed to rescue the majority of neurocognitive phenotypes in a murine AS model.