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Unexpected effects of ivermectin and selamectin on inducible CreER activity in mice
Peter A Kropp1,2, Gabrielle V Rushing3, Asa A Brockman4
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN USA.
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.
Insights
Common anti-parasitics ivermectin and selamectin can alter Cre recombinase activity in transgenic mice. This unintended effect may impact gene inactivation studies, requiring careful consideration during treatment of pregnant mice.
Area of Science:
- Genetics
- Pharmacology
- Animal Research
Background:
- Anti-parasitic drugs like ivermectin and selamectin are widely used in research animal facilities for common infections.
- These drugs are often presumed safe for research animals and their transgenic elements.
- Previous evidence suggests ivermectin can activate Cre recombinase activity.
Observation:
- This study investigated the effect of ivermectin and selamectin on Cre recombinase activity in transgenic mice.
- Offspring from dams treated with these anti-parasitics during pregnancy and nursing were analyzed.
- Reporter genes co-expressed with independently generated CreER drivers were examined.
Findings:
- Both ivermectin and selamectin were found to alter Cre recombinase activity.
- These alterations suggest potential unintended consequences for gene inactivation studies in mice.
- The study observed changes in transgene activity in offspring exposed to these drugs in utero and via lactation.
Implications:
- The precise mechanisms of ivermectin and selamectin on CreER activity require further investigation.
- Treatment of pregnant transgenic mice with these anti-parasitics can significantly affect transgene activity in offspring.
- Researchers must carefully consider the use of ivermectin and selamectin when working with transgenic mouse models to avoid confounding experimental results.
