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
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Slye, M. The incidence and inheritability of spontaneous tumors in Mice: (Second report.). J. Med. Res. 30, 281–298 (1914).
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).
Strong, L. C. in Origins of Inbred Mice (ed. Morse, H. C.) (Academic Press, New York, 1978).
Heston, W. E. Genetic analysis of susceptibilty to induced pulmonary tumors in mice. J. Natl Cancer Inst. 3, 69–78 (1942).
Heston, W. E. Relationship between susceptibility to induced pulmonary tumors and certain known genes in mice. J. Natl Cancer Inst. 2, 127–132 (1942).
Capecchi, M. R. Altering the genome by homologous recombination. Science 244, 1288–1292 (1989).
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).
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).
McGlynn, K. A. et al. Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. Cancer Res. 63, 4594–4601 (2003).
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).
Quigley, D. A. et al. Genetic architecture of mouse skin inflammation and tumour susceptibility. Nature 458, 505–508 (2009).
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).
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).
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).
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).
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).
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).
Park, Y. G. et al. Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nature Genet. 37, 1055–1062 (2005).
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).
Crawford, N. P. et al. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis. PLoS Genet. 3, e214 (2007).
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).
Darvasi, A. Experimental strategies for the genetic dissection of complex traits in animal models. Nature Genet. 18, 19–24 (1998).
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).
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).
Bailey, D. in The Mouse in Biomedical Research (ed. Fox, J.) 223–239 (Academic, New York, 1981).
Churchill, G. A. et al. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nature Genet. 36, 1133–1137 (2004).
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).
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).
Crawford, N. P. et al. Bromodomain 4 activation predicts breast cancer survival. Proc. Natl Acad. Sci. USA 105, 6380–6385 (2008).
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).
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
Corresponding author
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights 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
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrc3206
This article is cited by
-
Mechanisms of breast cancer metastasis
Clinical & Experimental Metastasis (2022)
-
Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer
Cancer and Metastasis Reviews (2018)
-
Optimizing mouse models for precision cancer prevention
Nature Reviews Cancer (2016)
-
Advancements in Modeling Colorectal Cancer in Rodents
Current Colorectal Cancer Reports (2016)
-
In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci
Mammalian Genome (2015)