Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Note
  • Published:

Effects of housing density on nasal pathology of breeding mice housed in individually ventilated cages

Lab Animal volume 41, pages 68–76 (2012)Cite this article

Abstract

The 2011 edition of the Guide for the Care and Use of Laboratory Animals includes new recommendations for the amount of floor space that should be provided to breeding mice. When pairs or trios of continuously breeding mice are housed in shoebox cages, they may have less than this recommended amount of floor space. High housing densities may adversely affect animal health, for example, by compromising air quality inside the cage. Hence, some institutions are carefully reevaluating the microenvironments of breeding cages. The use of individually ventilated cages (IVCs) to house research mice allows for greater control over the quality of the cage microenvironment. The authors evaluated the microenvironments of shoebox cages in an IVC rack system housing breeding and non-breeding Swiss Webster mice. Ammonia concentrations were significantly higher in cages housing breeding trios with two litters. Histopathologic lesions attributable to inhaled irritants such as ammonia were found in mice housed in breeding pairs and trios. The authors conclude that the microenvironments of cages in an IVC rack system housing breeding pairs and trios may be detrimental to animal health.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Average intracage temperature and relative humidity increased over time in all breeding cages.
Figure 2: Average intracage NH3 concentrations increased over time in all occupied cages, and average intracage CO2 concentrations increased over time only in breeding cages.
Figure 3: Nasal pathology in an adult mouse from a breeding trio.

Similar content being viewed by others

References

  1. Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals 7th edn. (National Academies Press, Washington, DC, 1996).

  2. Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals 8th edn. (National Academies Press, Washington, DC, 2011).

  3. Davidson, L.P., Chedester, A.L. & Cole, M.N. Effects of cage density on behavior in young adult mice. Comp. Med. 57, 355–359 (2007).

    CAS  PubMed  Google Scholar 

  4. Eveleigh, J.R. Murine cage density: cage ammonia levels during the reproductive performance of an inbred strain and two outbred stocks of monogamous breeding pairs of mice. Lab. Anim. 27, 156–160 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Laber, K., Veatch, L.M., Lopez, M.F., Mulligan, J.K. & Lathers, D.M. Effects of housing density on weight gain, immune function, behavior, and plasma corticosterone concentrations in BALB/c and C57BL/6 mice. J. Am. Assoc. Lab. Anim. Sci. 47, 16–23 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Nicholson, A. et al. The response of C57BL/6J and BALB/cJ mice to increased housing density. J. Am. Assoc. Lab. Anim. Sci. 48, 740–753 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Smith, A.L., Mabus, S.L., Stockwell, J.D. & Muir, C. Effects of housing density and cage floor space on C57BL/6J mice. Comp. Med. 54, 656–663 (2004).

    CAS  PubMed  Google Scholar 

  8. Smith, A.L., Mabus, S.L., Muir, C. & Woo, Y. Effects of housing density and cage floor space on three strains of young adult inbred mice. Comp. Med. 55, 368–376 (2005).

    CAS  PubMed  Google Scholar 

  9. O'Malley, J., Dambrosia, J.M. & Davis, J.A. Effect of housing density on reproductive parameters and corticosterone levels in nursing mice. J. Am. Assoc. Lab. Anim. Sci. 47, 9–15 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Reeb-Whitaker, C.K. et al. The impact of reduced frequency of cage changes on the health of mice housed in ventilated cages. Lab. Anim. 35, 58–73 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Lipman, N.S., Corning, B.F. & Coiro, M.A. Sr. The effects of intracage ventilation on microenvironmental conditions in filter-top cages. Lab. Anim. 26, 206–210 (1992).

    Article  CAS  PubMed  Google Scholar 

  12. Lipman, N.S. Isolator rodent caging systems (state of the art): a critical view. Contemp. Top. Lab. Anim. Sci. 38, 9–17 (1999).

    PubMed  Google Scholar 

  13. Höglund, A.U. & Renström, A. Evaluation of individually ventilated cage systems for laboratory rodents: cage environment and animal health aspects. Lab. Anim. 35, 51–57 (2001).

    Article  PubMed  Google Scholar 

  14. Reeb, C. et al. Microenvironment in ventilated animal cages with differing ventilation rates, mice populations, and frequency of bedding changes. Contemp. Top. Lab. Anim. Sci. 37, 43–49 (1998).

    PubMed  Google Scholar 

  15. Gamble, M.R. & Clough, G. Ammonia build-up in animal boxes and its effect on rat tracheal epithelium. Lab. Anim. 10, 93–104 (1976).

    Article  CAS  PubMed  Google Scholar 

  16. Krohn, T.C. & Hansen, A.K. The effects of and tolerance for carbon dioxide in relation to recent developments in laboratory animal housing. Scand. J. Lab. Anim. Sci. 27, 173–181 (2000).

    Google Scholar 

  17. Burn, C.C., Peters, A., Day, M.J. & Mason, G.J. Long-term effects of cage-cleaning frequency and bedding type on laboratory rat health, welfare, and handleability: a cross-laboratory study. Lab. Anim. 40, 353–370 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Hasenau, J.J., Baggs, R.B. & Kraus, A.L. Microenvironments in microisolation cages using BALB/c and CD-1 mice. Contemp. Top. Lab Anim. Sci. 32, 11–16 (1993).

    Google Scholar 

  19. Perkins, S.E. & Lipman, N.S. Characterization and quantification of microenvironmental contaminants in isolator cages with a variety of contact beddings. Contemp. Top. Lab. Anim. Sci. 34, 93–98 (1995).

    CAS  PubMed  Google Scholar 

  20. Perkins, S.E. & Lipman, N.S. Evaluation of microenvironmental conditions and noise generation in three individually ventilated rodent caging systems and static isolator cages. Contemp. Top. Lab. Anim. Sci. 35, 61–65 (1996).

    CAS  PubMed  Google Scholar 

  21. Rosenbaum, M.D., VandeWoude, S. & Johnson, T.E. Effects of cage-change frequency and bedding volume on mice and their microenvironment. J. Am. Assoc. Lab. Anim. Sci. 48, 763–773 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Silverman, J., Bays, D.W., Cooper, S.F. & Baker, S.P. Ammonia and carbon dioxide concentrations in disposable and reusable ventilated mouse cages. J. Am. Assoc. Lab. Anim. Sci. 47, 57–62 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Silverman, J., Bays, D.W. & Baker, S.P. Ammonia and carbon dioxide concentrations in disposable and reusable static mouse cages. Lab Anim. (NY) 38, 16–23 (2009).

    Article  Google Scholar 

  24. Serrano, L.J. Carbon dioxide and ammonia in mouse cages: effect of cage covers, population, and activity. Lab. Anim. Sci. 21, 75–85 (1971).

    CAS  PubMed  Google Scholar 

  25. Greiner, T. Indoor air quality: carbon monoxide and carbon dioxide. Department of Agricultural and Biosystems Engineering, Iowa State University. (1995). http://www3.abe.iastate.edu/human_house/aen125.asp.

    Google Scholar 

  26. Broderson, J.R., Lindsey, J.R. & Crawford, J.E. The role of environmental ammonia in respiratory mycoplasmosis of rats. Am. J. Pathol. 85, 115–128 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Green, A.R., Wathes, C.M., Demmers, T.G., Clark, J.M. & Xin, H. Development and application of a novel environmental preference chamber for assessing responses of laboratory mice to atmospheric ammonia. J. Am. Assoc. Lab. Anim. Sci. 47, 49–56 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Godbey, T., Gray, G. & Jeffery, D. Cage-change interval preference in mice. Lab Anim. (NY) 40, 225–230 (2011).

    Article  Google Scholar 

  29. Buckley, L.A., Jiang, X.Z., James, R.A., Morgan, K.T. & Barrow, C.S. Respiratory tract lesions induced by sensory irritants at the RD50 concentration. Toxicol. Appl. Pharmacol. 74, 417–429 (1984).

    Article  CAS  PubMed  Google Scholar 

  30. Tepper, J.S., Weiss, B. & Wood, R.W. Alterations in behavior produced by inhaled ozone or ammonia. Fundam. Appl. Toxicol. 5, 1110–1118 (1985).

    Article  CAS  PubMed  Google Scholar 

  31. Schaerdel, A.D., White, W.J., Lang, C.M., Dvorchik, B.H. & Bohner, K. Localized and systemic effects of environmental ammonia in rats. Lab. Anim. Sci. 33, 40–45 (1983).

    CAS  PubMed  Google Scholar 

  32. Danneman, P.J., Stein, S. & Walshaw, S.O. Humane and practical implications of using carbon dioxide mixed with oxygen for anesthesia or euthanasia of rats. Lab Anim. Sci. 47, 376–385 (1997).

    CAS  PubMed  Google Scholar 

  33. Feldman, D.B. & Gupta, B.N. Histopathologic changes in laboratory animals resulting from various methods of euthanasia. Lab Anim. Sci. 26, 218–221 (1976).

    CAS  PubMed  Google Scholar 

  34. Burkholder, T.H. et al. Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart rate, and respiratory lesions in rats. J. Am. Assoc. Lab. Anim. Sci. 49, 448–453 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Office of Laboratory Animal Welfare. Frequently Asked Questions: May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density? PHS Policy on Humane Care and Use of Laboratory Animals. http://grants.nih.gov/grants/olaw/faqs.htm#f10.

  36. Jacoby, R.O., Fox, J.G. & Davisson, M. in Laboratory Animal Medicine 2nd edn. (eds. Fox, J.G., Anderson, L.C., Loew, F.M. & Quimby, F.W.) 35–120 (Academic, New York, 2002).

    Book  Google Scholar 

  37. Ryu, J., Heldt, G.P., Nguyen, M., Gavrialov, O. & Haddad, G.G. Chronic hypercapnia alters lung matrix composition in mouse pups. J. Appl. Physiol. 109, 203–210 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nielson, G.D., Petersen, S.H., Vinggaard, A.M., Hansen, L.F. & Wolkoff, P. Ventilation, CO2 production, and CO2 exposure effects in conscious, restrained CF-1 mice. Pharmacol. Toxicol. 72, 163–168 (1993).

    Article  Google Scholar 

  39. Gaafar, H., Girgis, R., Hussein, M. & el-Nemr, F. The effect of ammonia on the respiratory nasal mucosa of mice. A histological and histochemical study. Acta Otolaryngol. 112, 339–342 (1992).

    Article  CAS  PubMed  Google Scholar 

  40. Harkema, J.R. Comparative aspects of nasal airway anatomy: relevance to inhalation toxicology. Toxicol. Pathol. 19, 321–336 (1991).

    Article  CAS  PubMed  Google Scholar 

  41. McInnes, E.F. & Miller, R.A. A review of upper respiratory tract inhalation pathology. Comp. Clin. Pathol. 16, 215–222 (2007).

    Article  Google Scholar 

Download references

Acknowledgements

This study was funded by the Animal Resource at the University of Rochester. We thank Dan DeMagistris and April Tirabassi for their assistance in experimental set-up and MaryKay Austin, Linda Johnstone and Michelle Streamer for their technical skill and expertise.

Author information

Authors and Affiliations

  1. Department of Comparative Medicine, University of Rochester, Rochester, NY

    Louis DiVincenti Jr.,  Diane Moorman-White &  Jeff Wyatt

  2. Department of Biostatistics, University of Rochester, Rochester, NY

    Nikolay Bavlov

  3. Northwest ZooPath, Monroe, WA

    Michael Garner

Authors
  1. Louis DiVincenti Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diane Moorman-White
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikolay Bavlov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Garner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeff Wyatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Louis DiVincenti Jr..

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

DiVincenti, L., Moorman-White, D., Bavlov, N. et al. Effects of housing density on nasal pathology of breeding mice housed in individually ventilated cages. Lab Anim 41, 68–76 (2012). https://doi.org/10.1038/laban0312-68

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban0312-68

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing