Abstract
BackgroundAnti-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 presentationWe 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.ConclusionsAlthough 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.
Highlights
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
In all cases, unexpected tdTomato-positive cells were located within regions that would normally be targeted by the relevant transgenic CreER line. These findings are consistent with those of Corbo-Rodgers et al in that ivermectin, and in this additional case selamectin, treatment can aberrantly induce CreER activity in the absence of tamoxifen administration. Discussion and conclusions these studies are limited in their scope, they both indicate that the highly-related antihelmitic drugs ivermectin and selamectin can alter the tamoxifenindependent activity of CreER fusion proteins in the offspring of treated dams
In the case of both Emx1-CreER and Gli1-CreER, recombinase activity was abberantly activated in the absence of tamoxifen
Summary
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. Helminth infection is one of the most common types of parasitic infection in laboratory rodents Normally benign, these infections can eventually cause secondary effects including, but not limited to, heightening the host animal’s immune system. These infections can eventually cause secondary effects including, but not limited to, heightening the host animal’s immune system Such effects can not Amongst the most common treatments for helminthic parasitic infections are the pharmacological agents ivermectin and selamectin. The commonly held belief is that ivermectin has minimal effect on mammalian systems and can be used without ill-effect on rodent colonies during ongoing pre-clinical studies While this understanding of the safety of ivermectin appears to hold true in most circumstances, there is evidence that ivermectin treatment can have unintended effects on certain transgenic elements [4]. Known as a CreER, this fusion protein is activated upon the administration of tamoxifen, an estrogen analog, resulting in translocation of the CreER protein to the nucleus where it mediates DNA recombination at specific sequences known as loxP sites introduced into the desired locus
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