The ferret's susceptibility to influenza viruses has been well documented and characterized, and the species has increasingly contributed to the understanding of influenza pathogenesis and transmission, and to the development of new vaccines and antivirals. In response to growing demand for ferrets seronegative for influenza, Marshall BioResources has established two barrier breeding facilities with many provisions to ensure the health and welfare of the ferrets, including that they remain free of influenza and other pathogens.
Ferret influenza models
Ferrets have been proven to be a valuable model for studying many viral infections, most notably influenza. The first report of successful infection of ferrets with influenza was documented in 1933 by Smith, Andrewes and Laidlaw1. Ferrets are frequently used to evaluate the efficacy and the safety of new influenza vaccines2, and ferrets are also valuable for evaluating the efficacy of antivirals as well3.
While mice are the most commonly used animal for testing antivirals, the disadvantage is that they do not present clinical symptoms such as fevers, sneezing and further respiratory disease following infection with influenza. Ferrets, on the other hand, do naturally display symptoms similar to humans following infection, and viral modifications are not required to infect ferrets with common human and avian strains3,4,5,6. Currently, the ferret is the only small mammal that allows for investigation of both influenza pathogenesis and transmission within the same species2,5.
According to a recent review by Oh & Hurt, the number of influenza publications that cite ferrets has been increasing since 2008 (ref. 3). However, availability of animals, especially those seronegative for influenza, has been noted as a disadvantage of the ferret model2,7. Because new influenza viruses continually emerge, some with pandemic potential, there is an ongoing need for a steady supply of seronegative ferrets. Therefore, Marshall BioResources now maintains two barrier ferret-breeding facilities, one in the United States and one in the United Kingdom, to provide influenza-free ferrets globally.
Influenza-free barrier facilities
Specific pathogen-free ferrets are bred and raised within barrier facilities located at Marshall BioResources' operations in New York and East Yorkshire. The seronegative status of the ferrets is maintained through the implementation of several features.
People: Access to the breeding barriers is strictly limited. The use of key cards and access codes ensures only necessary personnel access the animal space. Employees are prohibited from entering the facility for 48 hours following contact with other ferrets, and staff are required to receive annual influenza vaccination. People entering the facility take a full shower before changing into facility issued clothing and footwear. Gloves, hair covers, N-95 masks and Stryker hoods are worn by all staff while inside the barrier (Fig. 1).
Supplies: The movement of materials in and out of the facilities is also tightly controlled through the use of airlocks with electric strikes and magnetic locks. Materials are sanitized using Virkon™ S or hydrogen peroxide fog in the US, and Anigene and Neopredisan in the UK. Feed arrives irradiated and the packaging is sanitized before it enters the facility; bedding is also irradiated or autoclaved.
Water and air: Water is supplied from a municipal source. In the UK, water is double filtered to 0.2 microns, and in the US it is coarse filtered followed by UV irradiation. Air is coarse and HEPA filtered, and in the US this is followed by UV irradiation as well. There is positive pressure within the animal rooms with no re-circulation of air and ∼10 air changes per hour.
Environmental parameters are monitored continuously by an automated Energy Management System and generators are in place in the event of a power outage to ensure the barrier remains pressurized and the health status is maintained.
Housing and care of ferrets
There are few standards that specifically address the care and welfare of ferrets8. Therefore, Marshall BioResources has relied mostly on decades of experience. Ferrets are incredibly social and gregarious, therefore group housing is easy to maintain. Mature males can be sexually aggressive towards each other, which can limit social housing efforts. However, current efforts are ongoing to evaluate options for reducing this aggression among socially housed males.
Enrichment at Marshall BioResources includes vertical complexity and promotes species typical behaviors such as digging, burrowing and chasing. All ferrets are provided dropped nest pans with bedding (Fig. 2a), and additional enrichment such as hammocks, tubes, “jingle balls” and other toys are also utilized (Fig. 2b–d). Chunks of bedding material provide a great way to facilitate digging and burrowing behaviors (Fig. 2a). The enrichment program at Marshall BioResources is also continually evolving to ensure it remains effective.
Housing pens are made of stainless steel with no openings over 1 in2. Ferrets are fed ad libitum via J-Feeders affixed to the pens. Primary and secondary enclosures, including nest pans and toys, are sanitized using Virkon S or 7% chlorine bleach.
Ferrets are very sensitive to the photo period, and their reproductive behavior is highly influenced by the light cycle. Most animals within the breeding colony are kept at 16 hours light:8 hours dark to simulate breeding season. There is also housing space available with the opposite light cycle; the animals housed in this space can include mature ferrets that are not actively breeding. Females are especially sensitive and can remain in persistent estrous with negative health impacts if kept in long light cycles when they are not breeding or nursing9,10.
Unlike other species, there are no current recommendations for the health monitoring of ferrets. Therefore, Marshall BioResources worked with consultants and researchers to develop a comprehensive health monitoring program for the ferret colonies.
Marshall has been raising ferrets since 1939 for a variety of purposes: for trapping rabbits, for hunting pests, as pets, and for biomedical research. Marshall continues to be a leading supplier of ferret models for research, as well as pet ferrets. Along with ferrets, Marshall BioResources also provides Marshall Beagles, Göttingen Minipigs, Mongrels & Hounds, IFN Knockout Mice (A129 & AG129), SPF Guinea Pigs, and related services for biomedical research. Marshall demonstrates a deep commitment to animal health and welfare, and to the advancement of science and medicine. For more information about Marshall and for contact information please visit http://www.marshallbio.com.
Smith, W., Andrewes, C.H. & Laidlaw, P.P. A virus obtained from influenza patients. The Lancet 222, 66–68 (1933).
Margine, I. & Krammer, F. Animal models for influenza viruses: Implications for universal vaccine development. Pathogens 3, 845–874 (2014).
Oh, D.Y. & Hurt, A.C. Using the ferret as an animal model for investigating influenza antiviral effectiveness. Front. Microbiol. 7, 1–12 (2016).
Matsuoka, Y., Lamirande, E.W. & Subbarao, K. The ferret model for influenza. Curr. Protoc. Microbiol. Suppl. 13, 15G.2.1–15G.2.29 (2009).
Belser, J.A., Katz, J.M. & Tumpey, T.M. The ferret as a model organism to study influenza A virus infection. Dis. Model. Mech. 4, 575–579 (2011).
Xu, L. et al. The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus. Virol. J. 10, 253–260 (2013).
Maher, J.A. & DeStefano, J. The ferret: an animal model to study influenza virus. Lab Anim. (NY). 33, 50–53 (2004).
Marini, R.P. Regulatory considerations. in Biology and Diseases of the Ferret 3rd ed. (eds. Fox, J.G. & Marini, R.P.) 211–217 (John Wiley & Sons, Ames, IA, 2014).
Fox, J.G., Bell, J.A. & Broom, R. Growth and reproduction. in Biology and Diseases of the Ferret 3rd ed. (eds. Fox, J.G. & Marini, R.P.) 187–209 (John Wiley & Sons, Ames, IA, 2014).
Ball, R.S. Husbandry and management of the domestic ferret. Lab Anim. (NY). 31, 37–42 (2002).
This article was submitted to Lab Animal by a commercial organization and has not been peer-reviewed. Lab Animal takes no responsibility for the accuracy or relevancy of the information provided therein.