A deletion of chromosome 16p11.2 has been shown to underlie 1% of all autism cases as well as several other developmental disorders including ADHD. The major vault protein (MVP) is a gene that resides within the deleted region of 16p11.2 which is traditionally known to confer drug resistance in the lung - the role of MVP in the brain, however, is unknown. Mice heterozygous (HET) for MVP display reduced cortical plasticity during monocular deprivation (MD) and knockout (KO) mice display hyperactivity (Nagakura et al., unpublished). We hypothesized that MVP is localized at synapses to regulate either presynaptic vesicular transporters or postsynaptic receptors. To this end, we isolated the synaptic compartments (synaptoneurosomes) of wild type (WT), HET, and KO mice and performed western blots to measure the expression levels of MVP, vesicular proteins, and postsynaptic receptors (such as SV2, NR1, GluA1). MVP is expressed equally in the synaptoneurosomes and whole homogenates of WT mice, suggesting that MVP plays some role(s) at the synapse. Nevertheless, the levels of receptors and vesicular proteins were not statistically different among WT, HET, and KO mice. Future directions include testing activity-dependent regulation of receptor levels as affected by MD.

Synaptic role of the major vault protein in developmental disorders

247th National Meeting (2014)

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