Sex-biasing influence of autism-associated <i>Ube3a</i> gene overdosage at connectomic, behavioral, and transcriptomic levels.

ABSTRACT: Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene (Ube3a) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of Ube3a via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of Ube3a may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q dupli

SUBMITTER: Montani C 

PROVIDER: S-EPMC11244557 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature