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GEN recently spoke to Guy Mulder, DVM, Executive Director, Veterinary and Professional Service at Charles River Laboratories, to get the inside scoop on animal model production and the added value that commercial vendors provide.
GEN: Biosecurity planning and preparedness are vital to maintain the health and integrity of animal colonies. Can you share some insights on how to insulate lab facilities against unforeseen variables?
Mulder: Research animals like mice and rats are affected by environmental and genetic factors which can alter their phenotypes and impact research outcomes and consequently affect reproducibility of experimental results.
To prevent the introduction of unwanted infectious agents into research colonies, specially designed biosecurity programs encompass practices to identify all possible contamination sources along with mitigation steps to eradicate risks.
Infectious agents can impact research outcomes and reproducibility. Bacterial agents, such as Salmonella, can cause clinical disease, while transient or chronic viral agents may not cause overt symptoms. However, during replication, viruses alter physiology at the cellular or animal level.
A biosecurity program’s key aspects include daily husbandry practices, e.g., the use of PPE, sterilization, and disinfection along with routine QC to validate the processes’ effectiveness.
Continual health monitoring provides frequent validation of the health status of production colonies and protects against enrolling animals with unwanted infectious agents in studies.
Animals from commercial vendors with strong track records of health and genetic quality can be brought directly into facilities with confidence. When genetically modified animals are obtained from other investigators and noncommercial sources, an intake process should quarantine and test animals to confirm that a facility’s internal health standards are met before release into general use.
GEN: Genetic drift affects the reproducibility of research. What are some ways to mitigate its impact on animal colonies?
Mulder: We include genetic management and genetic testing in our biosecurity program. Visual observation alone is inadequate to verify animals meet a specific genetic profile.
Inbred strains are designed to be genetically homogeneous. Accidental contamination or spontaneous mutations can corrupt integrity. To address drift, every 10 generations, we transfer genetics from one foundation “gold standard” colony to our inbred colonies globally and also monitor these colonies quarterly using strain-specific SNP panels.
Pedigree tracking ensures brother and sister mating and is trackable back to a founding strain progenitor. In addition to frequent genetic testing, the overlaying QC program also includes comprehensive records review by independent QA personnel to ensure adherence to colony management and breeding standards.
Outbred models are designed to have a high level of genetic heterogeneity. Oversight QC, rotating breeding schemes to prevent inbreeding, and an annual genetic testing program ensure genetic integrity.
GEN: Help us understand the evaluation process when considering and comparing sourcing commercially available animal models to in-house breeding.
Mulder: I recommend auditing the commercial vendor, remotely or in person, to understand firsthand the strength and robustness of their biosecurity program and quality processes. Ask for colony health profile information and a description of their genetic management programs.
Most in-house bred lines are genetically modified models not commercially available. To free up research staff, we offer a genetically modified breeding service for contract breeding that maintains high quality standards and supplies animals as needed.
GEN: What are the implications of the 3Rs (Replace, Reduce, Refine), specifically reducing the number of animals bred which may not be required for study purposes?
Mulder: The greatest 3Rs opportunity is with common commercially produced strains. Commercial vendors serve a large population, increasing the likelihood that all animals will be utilized. Breeding small colonies in-house not only requires health and genetic management but also can produce a high level of waste if the research has a narrow specification, for example, males 6–8 weeks of age. Unless another researcher needs the female counterparts, half of the animals are excess.
Last year, we managed staffing levels and met production needs globally. Smaller institutions were more challenged—a large number of animals were not used as intended. Leveraging a partnership with a commercial vendor, especially for common models, addresses waste and allows research staff to concentrate on the science that cannot be outsourced.
Learn more about factors to consider when acquiring your animal models, including Biosecurity, Reproducibility, and “True Cost”: For a deeper dive visit our on-demand webinar: criver.com/considerthesource