, 2012). The alternative splicing of exons 19-20 and isoforms of SHANK2E (Y.-h.J., unpublished data), SHANK2A, and SHANK2B ( Lim et al., 1999) were conserved in mice but the status of SHANK2C

and other spliced exons has not been confirmed. Similar to SHANK3, the combination of different promoters and splicing is expected to produce substantial protein diversity of SHANK2 that may carry out distinct functions at synapses. Although similar complexity of transcriptional structure has been suggested for SHANK1 ( Figure 1C), detailed transcript profiles related to alternative promoters and exons remain to be delineated ( Lim et al., 1999). Together, the available evidence indicates that the overall VRT752271 chemical structure transcriptional structure of SHANK family genes is conserved in mice ( Wang et al., 2011). However, the complexity of transcriptional regulation poses a significant technical challenge to adequately model human SHANK mutations in mice. Mutant mice for all Shank family genes have now been produced and characterized ( Figure 3). Shank1 mutant mice with a deletion of exons 14–15 encoding the PDZ domain were first reported in 2008 ( Hung et al., 2008; Figure 3C), and more extensive behavioral analyses were conducted subsequently ( Silverman et al., 2011;

Wöhr et al., 2011). The targeted deletion of exons 14–15 is believed to produce a null allele of Shank1. Because the transcript structure has not been fully characterized, the possibility that this is not a complete Shank1 knockout cannot be ruled out. The major molecular and behavioral phenotypes of Shank1 mutant I-BET-762 supplier not mice are summarized in Table 3. The synaptic proteins GKAP/SAPAP and Homer are reduced in the PSD of Shank1−/− mouse brain. Smaller dendritic spines were observed, but the ultrastructure of the PSD is unaffected at CA1 synapses of Shank1−/− mice. Basal synaptic transmission was reduced but long-term potentiation (LTP) and long-term depression (LTD) in CA1 hippocampus were unaffected

( Hung et al., 2008). Behavioral analyses revealed subtle impairments in social interaction and communication as well as increased repetitive behaviors ( Silverman et al., 2011; Wöhr et al., 2011). Intriguingly, spatial learning and memory was enhanced in Shank1−/− mice ( Hung et al., 2008). Two different lines of Shank2 mutant mice have been recently reported ( Schmeisser et al., 2012; Won et al., 2012). Schmeisser et al. reported Shank2 exon 7 deletion mutant mice (Shank2 Δex7) while Won et al. described mice with both exons 6 and 7 deleted (Shank2 Δex6–7). Exons 6–7 encode the PDZ domain of Shank2. Importantly, the exon numbering is defined based on mouse Shank2a/ProSAP1a isoform cDNA (AB099695 or NM_00111373). Full-length mouse Shank2 mRNA has not been reported or deposited in a public database.