Mouse models of AS that recapitulate the major features of the disorder, including some ASD-like phenotypes, have been created and studied extensively. The first Ube3a mutant mice were created by making a targeted deletion of coding exon 2 (Jiang et al., 1998) and another model was created by disrupting last two coding exons 15–16 (Miura et al., 2002), but only the model with exon 2 deletion has been extensively studied subsequently. The brains of the maternally deficient (Ube3am−/p+) mice have significantly low or no detectable Ube3a protein, conferring high construct validity. Another group created mice that express either one extra (1xTg) or two extra copies (2xTg) of Ube3a, with reasonable construct validity for patients with maternally derived duplications and triplications in the genomic region encompassing UBE3A (Smith et al., 2011).
