Although there are no published studies that have explored the role of the Shank proteins in different cell types and brain regions using conditional knockouts, there have been considerable efforts to characterize the cellular phenotypes that result from the loss of these proteins. Deletion of Shank1 results in decreased spine density, shorter spines, and thinner PSDs in CA1 pyramidal neurons (Hung et al., 2008). However, both normal spine density (Won et al., 2012) and decreased spine density (Schmeisser et al., 2012) have been reported in hippocampal CA1 neurons from Shank2 mutants. Moreover, PSD length and thickness are not affected in CA1 neurons from either Shank2 line (Won et al., 2012; Schmeisser et al., 2012). Deletion of exons 13–16 of Shank3 led to decreased spine density, increased dendritic complexity, and thinner PSDs in medium spiny neurons (MSNs) of the striatum (Peça et al., 2011). However, deletion of exon 11 (Schmeisser et al., 2012) or exon 21 (Kouser et al, 2013) of Shank3 had no effect on either spine density nor on dendritic complexity in CA1 neurons. This may have been due
