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Evaluating Biosecurity of Physical Containment at USDA Animal Facilities to Prepare for Genetically Modified Rodent Trials
Abstract
House mice and rats have been introduced to most countries and islands worldwide and represent serious threats to biodiversity, economic enterprise, and human health. Genome editing and gene drives are being explored as new genetic biocontrol methods to effectively suppress rodent pests. An essential step in the translation of this technology to field-ready tools is to administer breeding and behavioral trials with freely-interacting genetically modified (GM) rodents. Due to the potential impacts of unintended release of GM organisms, these trials will require biosecure animal facilities that are rigorously tested to ensure physical containment. This study was conducted to develop and evaluate the biosecurity of a physical containment facility for house mouse trials at USDA’s National Wildlife Research Center. First, we conducted >20 trials with 75 wild-caught (non-GM) house mice to test their ability to escape from small containment units (0.35 m2). During these trials that lasted >160 days, mouse behaviors and escape attempts were documented following exposure to attractants (high value foods and potential mates) as motivators for escape. Just two mice successfully breached containment during early trials, and both were from chewing small holes in plastic walls that allowed escape to the other side of the containment unit. In a second series of trials, we assessed containment efficacy in a large (24 m2) arena intended to more closely replicate conditions of free-breeding wild mice. In these trials, mice were held in groups of six to 26 for up to 6 months. Across trials, only one mouse escaped the arena, an incident most likely attributable to human error during routine animal husbandry activities. This mouse was captured in the secondary containment (live-trap) within hours of breaching the primary containment. Overall, the containment strategy utilized here presents a robust design, with redundant containment mechanisms that should serve as a model for future behavioral trials using GM rodents. Additionally, our study highlights the need for rigorous staff training, careful attention to construction methods and materials, and adhering to biosecurity protocols to ensure the highest levels of containment that will be essential for testing efficacy of genetic biocontrols.
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