| First Author | Speed HE | Year | 2019 |
| Journal | eNeuro | Volume | 6 |
| Issue | 5 | PubMed ID | 31451607 |
| Mgi Jnum | J:288432 | Mgi Id | MGI:6432182 |
| Doi | 10.1523/ENEURO.0317-19.2019 | Citation | Speed HE, et al. (2019) Apparent Genetic Rescue of Adult Shank3 Exon 21 Insertion Mutation Mice Tempered by Appropriate Control Experiments. eNeuro 6(5):ENEURO.0317-19.2019 |
| abstractText | SHANK3 (ProSAP2) is among the most common genes mutated in autism spectrum disorders (ASD) and is the causative gene in Phelan-McDermid syndrome (PMS). We performed genetic rescue of Shank3 mutant phenotypes in adult mice expressing a Shank3 exon 21 insertion mutation (Shank3(G) ). We used a tamoxifen-inducible Cre/loxP system (Cre(Tam) ) to revert Shank3(G) to wild-type (WT) Shank3(+/+) We found that tamoxifen treatment in adult Shank3(G)Cre(Tam)+ mice resulted in complete rescue of SHANK3 protein expression in the brain and appeared to rescue synaptic transmission and some behavioral differences compared to Shank3(+/+)Cre(Tam)+ controls. However, follow-up comparisons between vehicle-treated, WT Cre-negative mice (Shank3(+/+)Cre(Tam)- and Shank3(+/+)Cre(Tam)+) demonstrated clear effects of Cre(Tam) on baseline synaptic transmission and some behaviors, making apparently positive genetic reversal effects difficult to interpret. Thus, while the Cre(Tam) tamoxifen-inducible system is a powerful tool that successfully rescues Shank3 expression in our Shank3(G/G) reversible mutants, one must exercise caution and use appropriate control comparisons to ensure sound interpretation. |
