Background: The developmental origins of Autism Spectrum Disorder (ASD) remain largely unknown. To begin to answer this question, a few studies have implemented conditional gene expression technology to induce or rescue ASD-causing mutations at different times during mouse development. Methods: In the current study, we crossed a ubiquitously-expressed inducible Cre line with mice containing loxP sites surrounding Shank3 exons 4-22 (Shank3 e4-22flox). We then delivered tamoxifen to determine the effects of disrupting Shank3 expression during two different time periods in development. Results: We found that reducing Shank3 expression in fully developed mice had minimal effects on behaviors that are characteristic of the conventional knockout mice. Similarly, disrupting Shank3 expression during an earlier time period (postnatal day 10-21) did not induce behaviors associated with germline deficiency. However, we observed differences in electrophysiological phenotypes for the two groups of conditional knockout mice. Conclusions: Because inducing mutations in adult mice or during early postnatal development is insufficient to cause ASD-like behaviors, Shank3 may play a role even earlier in development, but limited efficiency of the disruption could have contributed to our negative results. We also report considerable mortality when delivering tamoxifen across several different routes of administration, bringing further attention to caution the use of this type of conditional gene expression technology in future studies.
