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.

  • Opinion
  • Published:

Mouse models of cancer: does the strain matter?

Nature Reviews Cancer volume 12, pages 144–149 (2012)Cite this article

Subjects

Abstract

Mouse models are indispensible tools for understanding the molecular basis of cancer. However, despite the invaluable data provided regarding tumour biology, owing to inbreeding, current mouse models fail to accurately model human populations. Polymorphism is the essential characteristic that makes each of us unique humans, with different disease susceptibility, presentation and progression. Therefore, as we move closer towards designing clinical treatment that is based on an individual's unique biological makeup, it is imperative that we understand how inherited variability influences cancer phenotypes, how it can confound experiments and how it can be exploited to reveal new truths about cancer biology.

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: Potential genomic structures of genetically engineered mice based on an albino embryonic stem cell line.
Figure 2: Strategies to generate recombinant inbred panels and the Collaborative Cross.
Figure 3: Mating strategies for mapping cancer modifiers of GEM models using the Collaborative Cross.

Similar content being viewed by others

References

  1. Slye, M. The incidence and inheritability of spontaneous tumors in Mice: (Second report.). J. Med. Res. 30, 281–298 (1914).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Little, C. C. & Tyzzer, E. Further experimental studies on the inheritance of susceptibiilty to a transplantable tumor, carcinoma (J. W. A.) of the Japanese waltzing mouse. J. Med. Res. 33, 393–453 (1916).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Strong, L. C. in Origins of Inbred Mice (ed. Morse, H. C.) (Academic Press, New York, 1978).

    Google Scholar 

  4. Heston, W. E. Genetic analysis of susceptibilty to induced pulmonary tumors in mice. J. Natl Cancer Inst. 3, 69–78 (1942).

    Google Scholar 

  5. Heston, W. E. Relationship between susceptibility to induced pulmonary tumors and certain known genes in mice. J. Natl Cancer Inst. 2, 127–132 (1942).

    Google Scholar 

  6. Capecchi, M. R. Altering the genome by homologous recombination. Science 244, 1288–1292 (1989).

    Article  CAS  Google Scholar 

  7. Strunk, K. E., Amann, V. & Threadgill, D. W. Phenotypic variation resulting from a deficiency of epidermal growth factor receptor in mice is caused by extensive genetic heterogeneity that can be genetically and molecularly partitioned. Genetics 167, 1821–1832 (2004).

    Article  CAS  Google Scholar 

  8. Ghebranious, N. & Sell, S. The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice. Hepatology 27, 967–973 (1998).

    Article  CAS  Google Scholar 

  9. McGlynn, K. A. et al. Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. Cancer Res. 63, 4594–4601 (2003).

    CAS  PubMed  Google Scholar 

  10. Struewing, J. P. et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N. Engl. J. Med. 336, 1401–1408 (1997).

    Article  CAS  Google Scholar 

  11. Quigley, D. A. et al. Genetic architecture of mouse skin inflammation and tumour susceptibility. Nature 458, 505–508 (2009).

    Article  CAS  Google Scholar 

  12. Weber, J. L. & May, P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. Hum. Genet. 44, 388–396 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Pletcher, M. T. et al. Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse. PLoS Biol. 2, e393 (2004).

    Article  Google Scholar 

  14. Carlson, C. S. et al. Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am. J. Hum. Genet. 74, 106–120 (2004).

    Article  CAS  Google Scholar 

  15. Moser, A. R., Dove, W. F., Roth, K. A. & Gordon, J. I. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J. Cell Biol. 116, 1517–1526 (1992).

    Article  CAS  Google Scholar 

  16. MacPhee, M. et al. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. Cell 81, 957–966 (1995).

    Article  CAS  Google Scholar 

  17. Ewart-Toland, A. et al. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nature Genet. 34, 403–412 (2003).

    Article  CAS  Google Scholar 

  18. Park, Y. G. et al. Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nature Genet. 37, 1055–1062 (2005).

    Article  CAS  Google Scholar 

  19. Reilly, K. M. et al. Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc. Natl Acad. Sci. USA 101, 13008–13013 (2004).

    Article  CAS  Google Scholar 

  20. Crawford, N. P. et al. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis. PLoS Genet. 3, e214 (2007).

    Article  Google Scholar 

  21. Crawford, N. P. et al. Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer. Breast Cancer Res. 8, R16 (2006).

    Article  Google Scholar 

  22. Darvasi, A. Experimental strategies for the genetic dissection of complex traits in animal models. Nature Genet. 18, 19–24 (1998).

    Article  CAS  Google Scholar 

  23. Nadeau, J. H., Singer, J. B., Matin, A. & Lander, E. S. Analysing complex genetic traits with chromosome substitution strains. Nature Genet. 24, 221–225 (2000).

    Article  CAS  Google Scholar 

  24. de Koning, J. P., Mao, J. H. & Balmain, A. Novel approaches to identify low-penetrance cancer susceptibility genes using mouse models. Recent Res. Cancer Res. 163, 19–27; discussion 264–266 (2003).

    Article  CAS  Google Scholar 

  25. Bailey, D. in The Mouse in Biomedical Research (ed. Fox, J.) 223–239 (Academic, New York, 1981).

    Google Scholar 

  26. Churchill, G. A. et al. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nature Genet. 36, 1133–1137 (2004).

    Article  CAS  Google Scholar 

  27. Mucenski, M. L., Taylor, B. A., Jenkins, N. A. & Copeland, N. G. AKXD recombinant inbred strains: models for studying the molecular genetic basis of murine lymphomas. Mol. Cell Biol. 6, 4236–4243 (1986).

    Article  CAS  Google Scholar 

  28. Hunter, K. W. et al. Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res. 61, 8866–8872 (2001).

    CAS  PubMed  Google Scholar 

  29. Crawford, N. P. et al. Bromodomain 4 activation predicts breast cancer survival. Proc. Natl Acad. Sci. USA 105, 6380–6385 (2008).

    Article  CAS  Google Scholar 

  30. Crawford, N. P. et al. The Diasporin Pathway: a tumor progression-related transcriptional network that predicts breast cancer survival. Clin. Exp. Metastasis 25, 357–369 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I would like to thank J. Alsarraj and D. Threadgill for their insightful comments on this article. I would also like to apologize to the many investigators whose work was not discussed in this article owing to space constraints. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research.

Author information

Authors and Affiliations

  1. Kent W. Hunter is at the Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, 37/5046, 37 Convent Drive, Bethesda, Maryland 20892-4264, USA.,

    Kent W. Hunter

Authors
  1. Kent W. Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kent W. Hunter.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Kent W. Hunter's homepage

Collaborative Cross (CC) Status

Electronic Models Information, Communication, and Education

Mouse Genome Informatics

Mouse Phenome Database

Mouse Tumor Biology Database

Origins of Inbred Mice

Recombinant inbred (RI) strains

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hunter, K. Mouse models of cancer: does the strain matter?. Nat Rev Cancer 12, 144–149 (2012). https://doi.org/10.1038/nrc3206

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3206

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer