This is an individual National Research Service Award for post-doctoral research training, which provides support for promising Fellowship Applicants with the potential to become productive, independent investigators in scientific health-related research fields. Maternal (but not paternal) duplication of chromosome 15q11-13 is the most common copy number variation (CNV) causing autism spectrum disorder (ASD), present in 1-3% of all ASD cases. This CNV results in a child having too many copies of several genes. Of 40 genes in the chromosomal region, only UBE3A is expressed exclusively from the maternal chromosome in the brain. Angelman syndrome (AS), a disorder with opposite symptoms from ASD (e.g., hyper-social behavior vs. hypo-social behavior, respectively), is caused by a deletion of UBE3A, an E3 ubiquitin ligase. Given the gene's role in causing AS and the recent evidence implicating ubiquitin pathways in ASD pathophysiology, Ube3a may mediate ASD risk in 15q11-13 duplication. To test the potential role of UBE3A in autism, extra copies of the UBE3A gene will be inserted into mice to create a novel mouse model. First, behaviors directly relevant to ASD (social interaction, infant vocalization) will be characterized in the mice. Then molecular level investigations will ensue to determine how the UBE3A genes might lead to abnormal behaviors related to autism.