Unexpected effects of ivermectin and selamectin on inducible Cre(ER) activity in mice

BACKGROUND: Anti-parasitics are frequently used in research animal facilities to treat a multitude of common infections, with pinworms and fur mites being amongst the most common. Ivermectin and selamectin are common oral and topical treatments for these infections, respectively. Although commonly thought to be innocuous to both the research animals and any transgenic elements that the animals may carry, evidence exists that ivermectin is capable of activating the recombinase activity of at least one Cre(ER). The goal of the current study was to determine if there was an effect of either anti-parasitic agent on the activity of Cre(ER) proteins in transgenic mice. CASE PRESENTATION: We analyzed the offspring of transgenic mice exposed to either ivermectin or selamectin during pregnancy and nursing. Through analysis of reporter genes co-expressed with multiple, independently generated transgenic Cre(ER) drivers, we report here that ivermectin and selamectin both alter recombinase activity and thus may have unintended consequences on gene inactivation studies in mice. CONCLUSIONS: Although the mechanisms by which ivermectin and selamectin affect Cre(ER) activity in the offspring of treated dams remain unclear, the implications are important nonetheless. Treatment of pregnant transgenic mice with these anti-parasitics has the potential to alter transgene activity in the offspring. Special considerations should be made when planning treatment of transgenic mice with either of these pharmacologics.