Unexpected effects of ivermectin and selamectin on inducible Cre ER activity in mice
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Laboratory Animal Research
CASE REPORT
Open Access
Unexpected effects of ivermectin and selamectin on inducible CreER activity in mice Peter A. Kropp1,2* , Gabrielle V. Rushing3, Asa A. Brockman4, Erin N. Z. Yu5, Rebecca A. Ihrie3,4,6 and Maureen Gannon1,4,7,8
Abstract 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 CreER. The goal of the current study was to determine if there was an effect of either anti-parasitic agent on the activity of CreER 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 CreER 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 CreER 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. Keywords: Ivermectin, Selamectin, Transgenic mice, CreER
Background Helminth infection is one of the most common types of parasitic infection in laboratory rodents. Although normally benign, these infections can eventually cause secondary effects including, but not limited to, heightening the host animal’s immune system. Such effects can not * Correspondence: [email protected] 1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA 2 Present Address: Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20886, USA Full list of author information is available at the end of the article
only confound studies of the immune system, but also alter the activity of any exogenous treatment or genetic element potentially recognized as foreign. Given these complications, in addition to the obvious problem of parasite burden, treatment of laboratory rodent colonies for removal of parasites is imperative for institutional veterinary care and research alike. Amongst the most common treatments for helminthic parasitic infections are the pharmacological agents ivermectin and selamectin. Both drugs treat existing helminth infections by inducing
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