Peculiarities of Biomedical Experiments Involving Ferrets

DOI: 10.29296/2618723X-2019-02-10

K.L. Kryshen, А.Е. Katelnikova, M.N. Makarova, V.G. Makarov

Institute of Preclinical Studies
188663, Russia, Leningrad Region, Vsevolozhsky District, Kuzmolovsky Urban-Type Settlement, 3, Zavodskaya St., Build. 245,
Е-mail: [email protected]

Keywords: preclinical studies ferrets influenza virus maintenance basic manipulations body temperature measurement

For citation:

Kryshen K.L., Katelnikova А.Е., Makarova M.N., Makarov V.G. Peculiarities of Biomedical Experiments Involving Ferrets. Laboratory Animals for Science. 2019; 2.


Today ferrets are becoming increasingly popular in biomedical studies. Ferrets possess unique zootechnical characteristics, have a high susceptibility to virulent strains of the influenza virus and are most widely used in experimental studies to evaluate the immunogenic and protective properties of anti-influenza vaccines and the effectiveness of antiviral drugs. Influenza virus in ferrets causes infections that occur with clinical symptoms similar to those of a human infection (fever, runny nose, lethargy, weight loss, etc.). In addition, ferrets belong to predators, that may increase their value for preclinical studies as an animal species alternative to rodents. However, ferrets require special conditions and veterinary care. The purpose of this paper was to systematize the literature data and our own experience of working with ferrets in the laboratory. In an experimental vivarium, ferrets usually contain in cages with a height of at least 50 cm and a floor area depending on body weight from 1,500 to 6,000 cm2 per animal. Elements of the environment enrichment must be present in the cage such as hammocks, stairs, tunnels, balls. Environment temperature and humidity parameters for ferrets do not significantly differ from that for rodents. For ferrets that are used only in the experiment, a normal lighting cycle of 12 hours a day/12 hours a night is sufficient. Because ferrets are strict predators, they need a diet rich in protein and fat, but low in fiber. In the experiment most often used young adult male ferrets aged from 5 to 12 months, from 3 to 5 animals per group. Special attention in experimental work with ferrets should be given to anesthesia. Thus, the use of gas anesthesia, as a rule, is unacceptable, since repeated anesthesia during the experiment leads to marked changes in the lungs. One of the main parameters for assessing the development of influenza infection in ferrets is body temperature. The article proposes a method for measuring temperature with special implantable sensors, which allows to accurately and correctly analyse the dynamics of this parameter throughout the experiment.

Full text available only in Russian


  1. Voronin S. E., Makarova M. N., Kry`shen` K. L., Alyakrinskaya A. A., Ry`bakova A. V. Xor`ki, kak laboratorny`e zhivotny`e. Mezhdunarodny`j vestnik veterinarii. 2016; 2: 103–16.
  2. Fox J. G. Laboratory animal medicine. Elsevier. 2015.
  3. Gad S. C. Pigs and ferrets as models in toxicology and biological safety assessment. International journal of toxicology. 2000. Vol. 19 (3): 149–68. Doi: 10.1080/10915810050074928.
  4. Oh D.Y., Hurt A.C. Using the ferret as an animal model for investigating influenza antiviral effectiveness. Frontiers in microbiology. 2016. Vol. 7: 1–12. doi: 10.3389/fmicb.2016.00080.
  5. Maher J. A., DeStefano J. The ferret: an animal model to study influenza virus. Lab animal. 2004. Vol. 33; 9: 50–3. doi: 10.1038/laban1004-50.
  6. Rudenko L., Kiseleva I., Krutikova E., Stepanova E., Rekstin A., Donina S., Pisareva M., Grigorieva E., Kryshen K., Muzhikyan A., Makarova M., Sparrow E.G., Torelli G., Kieny M.P. Rationale for vaccination with trivalent or quadrivalent live attenuated influenza vaccines: Protective vaccine efficacy in the ferret model. PloS one. 13(12): e0208028. doi: 10.1371/journal.pone.0208028.
  7. Rudenko L., Kiseleva I., Krutikova E., Stepanova E., Isakova-Sivak I., Rekstin A., Pisareva M., Bazhenova E., Kotomina T., Katelnikova A., Muzhikyan A., Makarov V., Sparrow E.G., Torelli G. Two Live Attenuated Vaccines against Recent Low–and Highly Pathogenic H7N9 Influenza Viruses Are Safe and Immunogenic in Ferrets. Vaccines. 2018. Vol. 6(4): 1–18. doi: 10.3390/vaccines6040074
  8. Ng P.S., Bohm R., Hartley-Tassel, L. E., Steen J.A., Wang H., Lukowski S.W., Hawthorne P.L., Trezise A.E., Coloe P., Grimmond S.M., Haselhorst T., von Itzstein M., Paton A.W., Paton J.C., Jennings M.P. Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors. Nature communications. 2014. Vol. 5: 5750. doi: 10.1038/ncomms6750.
  9. Smith W., Smith, W., Andrewes, C. H., & Laidlaw, P. P. A virus obtained from influenza patients. Lancet. 1933. 222 (5732): 66–8. doi: 10.1016/S0140-6736(00)78541-2.
  10. Enkirch T., Von Messling V. Ferret models of viral pathogenesis. Virology. 2015.Vol.479-480: 259–70. doi: 10.1016/j.virol.2015.03.017
  11. Llojd M. Bolezni xor`kov. M.: Akvarium-Print. 2011: 208.
  12. Matchett, C. A., Marr, R., Berard, F. M., Cawthon, A. G., & Swing, S. P. The laboratory ferret. CRC Press. 2012.
  13. GOST 33217-2014 Rukovodstvo po soderzhaniyu i uxodu za laboratorny`mi zhivotny`mi. Pravila soderzhaniya i uxoda za laboratorny`mi xishhny`mi mlekopitayushhimi. 2016.
  14. Direktiva 2010/63/EU Evropejskogo Parlamenta i Soveta Evropejskogo soyuza ot 22 sentyabrya 2010 g. po oxrane zhivotny`x, ispol`zuemy`x v nauchny`x celyax.
  15. Belser J.A., Gustin K.M., Pearce M.B., Maines T.R., Zeng H., Pappas C., Sun X., Carney P.J., Villanueva J.M., Stevens J., Katz J.M., Tumpey T.M. Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature. 2013.501: 556–9. doi:10.1038/nature12391.
  16. Watanabe T., Kiso M., Fukuyama S., Nakajima N., Imai M., Yamada S., Murakami S., Yamayoshi S., Iwatsuki-Horimoto K., Sakoda Y., Takashita E., McBride R., Noda T., Hatta M., Imai H., Zhao D., Kishida N., Shirakura M., de Vries R.P., Shichinohe S., Okamatsu M., Tamura T., Tomita Y., Fujimoto N., Goto K., Katsura H., Kawakami E., Ishikawa I., Watanabe S., Ito M., Sakai-Tagawa Y., Sugita Y., Uraki R., Yamaji R., Eisfeld A.J., Zhong G., Fan S., Ping J., Maher E.A., Hanson A., Uchida Y., Saito T., Ozawa M., Neumann G., Kida H., Odagiri T., Paulson J.C., Hasegawa H., Tashiro M., Kawaoka Y. Characterization of H7N9 influenza A viruses isolated from humans. Nature. 2013. 501: 551–5. doi:10.1038/nature12392.
  17. Richard M., Schrauwen E.J., de Graaf M., Bestebroer T.M., Spronken M.I., van Boheemen S., de Meulder D., Lexmond P., Linster M., Herfst S., Smith D.J., van den Brand J.M., Burke D.F., Kuiken T., Rimmelzwaan G.F., Osterhaus A.D., Fouchier R.A. Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature. 2013. 501:560–3. doi:10.1038/nature12476.
  18. Xu L., Bao L., Deng W., Dong L., Zhu H., Chen T., Lv Q., Li F., Yuan J., Xiang Z., Gao K., Xu Y., Huang L., Li Y., Liu J., Yao Y., Yu P., Li X., Huang W., Zhao X., Lan Y., Guo J., Yong W., Wei Q., Chen H., Zhang L., Qin C. Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets. J Infect Dis. 2014. 209: 551–6. doi:10.1093/infdis/jit474.
  19. Rekstin A., Desheva Y., Kiseleva I., Ross T., Swayne D., Rudenko L. Live attenuated influenza H7N3 vaccine is safe, immunogenic and confers protection in animal models. The open microbiology journal. 2014. Vol. 8: 154-62. doi: 10.2174/1874285801408010154
  20. Ann J., Samant M., Rheaume C., Dumas C., Beaulieu E., Morasse A., Mallett C., Hamelin M.E., Papadopoulou B., Boivin G. Adjuvanted inactivated influenza A (H3N2) vaccines induce stronger immunogenicity in mice and confer higher protection in ferrets than unadjuvanted inactivated vaccines. Vaccine. 2014. Vol. 32(43): 5730–9. doi: 10.1016/j.vaccine.2014.08.029
  21. Smith J.H., Papania M., Knaus D., Brooks P., Haas D.L., Mair R., Barry J., Tompkins S.M., Tripp R.A. Nebulized live-attenuated influenza vaccine provides protection in ferrets at a reduced dose. Vaccine. 2012. Vol. 30 (19): 3026–33. doi: 10.1016/j.vaccine.2011.10.092
  22. Huang S.S., Banner D., Degousee N., Leon A.J., Xu L., Paquette S.G., Kanagasabai T., Fang Y., Rubino S., Rubin B., Kelvin D.J., Kelvin A.A. Differential pathological and immune responses in newly weaned ferrets are associated with a mild clinical outcome of pandemic 2009 H1N1 infection. J. Virol. 2012. Vol.86: 13187–201. doi:10.1128/JVI.01456-12.
  23. Paquette S.G., Huang S.S., Banner D., Xu L., Leomicronn A., Kelvin A.A., Kelvin D.J. Impaired heterologous immunity in aged ferrets during sequential influenza A H1N1 infection. Virology. 2014. 464-465: 177–83. doi: 10.1016/j.virol.2014.07.013
  24. Shen Z. Bowen R.A., Ge P., Yu J., Shen Y., Kong W., Jiang C., Wu J., Zhu C., Xu Y., Wei W., Rudenko L., Kiseleva I., Xu F. Evaluation of a candidate live attenuated influenza vaccine prepared in Changchun BCHT (China) for safety and efficacy in ferrets. Vaccine. 2016. Vol. 34 (48): 5953–8. doi: 10.1016/j.vaccine.2016.09.059
  25. Ellebedy A.H., Ducatez M.F., Duan S., Stigger-Rosser E., Rubrum A.M., Govorkova E.A., Webster R.G., Webby R.J. Impact of prior seasonal influenza vaccination and infection on pandemic A (H1N1) influenza virus replication in ferrets. Vaccine. 2011. Vol. 29 (17): 3335–9. doi: 10.1016/j.vaccine.2010.08.067
  26. Pushko P., Sun X., Tretyakova I., Hidajat R., Pulit-Penaloza J.A., Belser J. A., Maines T.R.., Tumpey T.M. Mono-and quadri-subtype virus-like particles (VLPs) containing H10 subtype elicit protective immunity to H10 influenza in a ferret challenge model. Vaccine. 2016. Vol. 34 (44): 5235–42. doi: 10.1016/j.vaccine.2016.09.012
  27. Pearce M.B., Belser J.A., Houser K.V., Katz J.M., Tumpey T.M. Efficacy of seasonal live attenuated influenza vaccine against virus replication and transmission of a pandemic 2009 H1N1 virus in ferrets. Vaccine. 2011. Vol. 29 (16): 2887–94. doi: 10.1016/j.vaccine.2016.09.012
  28. Ssy`lka na insturkciyu Zoletil 100

You may be interested