@article{6e33f88d705d47b5a2504941586b4d4b,
title = "Apparent genetic rescue of adult shank3 exon 21 insertion mutation mice tempered by appropriate control experiments",
abstract = "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 (Shank3G). We used a tamoxifen-inducible Cre/loxP system (CreTam) to revert Shank3G to wild-type (WT) Shank3/. We found that tamoxifen treatment in adult Shank3GCreTam 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/CreTam controls. However, follow-up comparisons between vehicle-treated, WT Cre-negative mice (Shank3/CreTam and Shank3/CreTam) demonstrated clear effects of CreTam on baseline synaptic transmission and some behaviors, making apparently positive genetic reversal effects difficult to interpret. Thus, while the CreTam tamoxifeninducible system is a powerful tool that successfully rescues Shank3 expression in our Shank3G/G reversible mutants, one must exercise caution and use appropriate control comparisons to ensure sound interpretation.",
keywords = "Autism, Cre-recombinase, Reversal, Shank3, Tamoxifen",
author = "Speed, {Haley E.} and Mehreen Kouser and Zhong Xuan and Shunan Liu and Anne Duong and Powell, {Craig M.}",
note = "Funding Information: This work was supported by United States Department of Health and Human Services National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development Grants R01HD069560 and R01HD069560-S1 (to C.M.P.), Autism Speaks (Autism Speaks Inc.) Grants (to C.M.P), Autism Speaks Grants (7666 to C.M.P, 7898 to H.E.S.) Autism Science Foundation Pre-doctoral Fellowship (to C.O.E.), The Hartwell Foundation (C.M.P.), Ed and Sue Rose Distinguished Professorship in Neurology (C.M.P.), BRAINS for Autism (C.M.P.), Virginia B. Spencer Endowed Chair at UAB (C.M.P.), and Dr. Clay Heighten and Dr. Debra Caudy (C.M.P.). C.M.P. has accepted travel funds and honoraria to speak once at each of the following companies: Psychogenics, Inc.; Astra-Zeneca; Roche; Pfizer; and Dainippon Sumitomo Pharma Co. C.M.P. also has investigator-initiated grant funding for clinical research with Novartis. *H.E.S. and M.K. contributed equally to this work. Funding Information: Acknowledgments: C.M.P. has accepted travel funds and honoraria to speak once at each of the following companies: Psychogenics, Inc.; Astra-Zeneca; Roche; Pfizer; and Dainippon Sumitomo Pharma Co. C.M.P. also has investigator-initiated grant funding for clinical research with Novartis. Publisher Copyright: {\textcopyright} 2019, Society for Neuroscience. All rights reserved.",
year = "2019",
month = sep,
day = "1",
doi = "10.1523/ENEURO.0317-19.2019",
language = "English (US)",
volume = "6",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society for Neuroscience",
number = "5",
}