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Unexpected effects of ivermectin and selamectin on inducible CreER activity in mice

Laboratory Animal Research 2020년 36권 1호 p.36 ~ 36
Kropp Peter A., Rushing Gabrielle V., Brockman Asa A., Yu Erin N. Z., Ihrie Rebecca A., Gannon Maureen,
소속 상세정보
 ( Kropp Peter A. ) - Vanderbilt University Department of Molecular Physiology and Biophysics
 ( Rushing Gabrielle V. ) - Vanderbilt University Neuroscience Program
 ( Brockman Asa A. ) - Vanderbilt University Department of Cell and Developmental Biology
 ( Yu Erin N. Z. ) - Vanderbilt University Medical Center Department of Pathology, Immunology and Microbiology
 ( Ihrie Rebecca A. ) - Vanderbilt University Neuroscience Program
 ( Gannon Maureen ) - Vanderbilt University Department of Molecular Physiology and Biophysics

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.

키워드

Ivermectin; Selamectin; Transgenic mice; CreER

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