• epilepsy

These investigations address whether UBE3A contributes to the seizure phenotypes associated with chromosome 15q duplication syndrome. The human UBE3A gene is within a chromosomal region susceptible to duplication, the 15q11-q13 region (see MIM:608636). These duplications result in a spectrum of variable phenotypes described as chromosome 15q11-q13 region duplication syndrome; phenotypes include autism, mental retardation, ataxia, seizures, developmental delays, and behavioral problems. See also the human disease model report 'autism spectrum disorder, susceptibility to, UBE3A-related' (FBhh0000515).

UBE3A encodes the ubiquitin protein ligase E3A, which acts in the ubiquitin proteasome pathway and as a transcriptional coactivator; the UBE3A gene is subject to genomic imprinting. There is a single orthologous gene in Drosophila, Dmel\Ube3a, for which classical amorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Multiple UAS constructs of the human Hsap\UBE3A gene have been introduced into flies, representing different protein isoforms of the wild-type UBE3A gene. Heterologous rescue (functional complementation) of loss-of-function larval learning defects has been demonstrated.

UBE3A is imprinted with maternal-specific expression in postnatal neurons, but not in glia. Thus, any phenotypes associated with glial expression may not be subject to imprinting. The consequences of glial overexpression of Dmel\Ube3a has been investigated in flies. A seizure-like phenotype (bang-induced paralysis) that worsens with age is observed in flies overexpressing Ube3a in glial cells; this phenotype is not observed when Ube3a is overexpressed in neurons. This system has been used to assess compounds that might allow pharmacological control of Ube3a-induced seizures.

[updated Oct. 2022 by FlyBase; FBrf0222196]