Currently, no conditional knockouts of Ube3a have been reported, so there is limited knowledge about what cell types and brain regions are involved in the behavioral abnormalities in Ube3am−/p+ mice. However, using mice engineered with a stop codon surrounded by loxP sites that prevents maternal Ube3a expression crossed with the commonly used ubiquitously-expressed inducible Cre line (CAG-Cre/Esr1), it was recently demonstrated that Ube3a reinstatement during embryonic or early postnatal development can prevent the expression of some ASD-like phenotypes, but reinstatement in mice later in development is not effective (Silva-Santos et al., 2015). Interestingly, these results are in contrast with those reported in Rett syndrome mice (see section 3.1). This could be due to the different behaviors reported in these studies, or it could indicate that some ASD susceptibility genes have tightly-regulated functions during development whereas others are required during the entire lifespan. Again, these types of studies need to be investigated using other models of ASDs before making any conclusions about the developmental time course of ASD pathogenesis.
