Skip to main content

Thank you for visiting 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.

The mouse ascending: perspectives for human-disease models

The laboratory mouse is widely considered the model organism of choice for studying the diseases of humans, with whom they share 99% of their genes. A distinguished history of mouse genetic experimentation has been further advanced by the development of powerful new tools to manipulate the mouse genome. The recent launch of several international initiatives to analyse the function of all mouse genes through mutagenesis, molecular analysis and phenotyping underscores the utility of the mouse for translating the information stored in the human genome into increasingly accurate models of human disease.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Large-scale strategy for mutagenesis of the mouse genome: a conditional knockout vector is created for each gene and introduced into mouse embryonic stem (ES) cells.
Figure 2: Principles of conditional mutation.


  1. Eisen, E. J. The Mouse in Animal Genetics and Breeding Research (World Scientific, Singapore, 2005).

    Book  Google Scholar 

  2. Paigen, K. One hundred years of mouse genetics: an intellectual history. I. The classical period (1902–1980). Genetics 163, 1–7 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Wade, C. M. & Daly, M. J. Genetic variation in laboratory mice. Nature Genet. 37, 1175–1180 (2005).

    CAS  Article  PubMed  Google Scholar 

  4. Oliver, P. L., Bitoun, E. & Davies, K. E. Comparative genetic analysis: the utility of mouse genetic systems for studying human monogenic disease. Mamm. Genome. doi: 10.1007/s00335-007-9014-8 (2007).

  5. Peters, L. L. et al. The mouse as a model for human biology: a resource guide for complex trait analysis. Nature Rev. Genet. 8, 58–69 (2007).

    CAS  Article  PubMed  Google Scholar 

  6. Shultz, L. D., Ishikawa, F. & Greiner, D. L. Humanized mice in translational biomedical research. Nature Rev. Immunol. 7, 118–130 (2007).

    CAS  Article  Google Scholar 

  7. Auwerx, J. et al. The European dimension for the mouse genome mutagenesis program. Nature Genet. 36, 925–927 (2004).

    CAS  Article  PubMed  Google Scholar 

  8. Nord, A. S. et al. The International Gene Trap Consortium Website: a portal to all publicly available gene trap cell lines in mouse. Nucleic Acids Res. 34, D642–D648 (2006).

    CAS  Article  PubMed  Google Scholar 

  9. Collins, F. S., Rossant, J. & Wurst, W. (International Mouse Knockout Consortium). A mouse for all reasons. Cell 128, 9–13 (2007).

    CAS  Article  PubMed  Google Scholar 

  10. Dupuy, A. J., Jenkins, N. A. & Copeland, N. G. Sleeping beauty: a novel cancer gene discovery tool. Hum. Mol. Genet. 15, R75–R79 (2006).

    CAS  Article  PubMed  Google Scholar 

  11. Cadinanos, J. & Bradley, A. Generation of an inducible and optimized piggyBac transposon system. Nucleic Acids Res. 35, e87 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wu, S., Ying, G., Wu, Q. & Capecchi, M. R. Toward simpler and faster genome-wide mutagenesis in mice. Nature Genet. 39, 922–930 (2007).

    CAS  Article  PubMed  Google Scholar 

  13. Cook, M. C., Vinuesa, C. G. & Goodnow, C. C. CENU-mutagenesis: insight into immune function and pathology. Curr. Opin. Immunol. 18, 627–633 (2006).

    CAS  Article  PubMed  Google Scholar 

  14. Ozanne, S. E. & Constancia, M. Mechanisms of disease: the developmental origins of disease and the role of the epigenotype. Nature Clin. Pract. Endocrinol. Metab. 3, 539–546 (2007).

    CAS  Article  Google Scholar 

  15. Feinberg, A. P. Phenotypic plasticity and the epigenetics of human disease. Nature 447, 433–440 (2007).

    CAS  Article  PubMed  Google Scholar 

  16. ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816 (2007).

  17. O'Carroll, D., Mecklenbrauker, I., Das, P. P., Santana, A., Koenig, U., Enright, A. J., Miska, E. A., Tarakhovsky, A. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. doi:10.1101/gad.1565607 (2007).

  18. Georges, M., Coppieters, W. & Charlier, C. Polymorphic miRNA-mediated gene regulation: contribution to phenotypic variation and disease. Curr. Opin. Genet. Dev. 17, 166–176 (2007).

    CAS  Article  PubMed  Google Scholar 

  19. Deidda, G., Rossi, N. & Tocchini-Valentini, G. P. An archaeal endoribonuclease catalyses cis- and trans-nonspliceosomal splicing in mouse cells. Nature Biotechnol. 21, 1499–504 (2003).

    CAS  Article  Google Scholar 

  20. Gailus-Durner, V. et al. Introducing the German Mouse Clinic: open access platform for standardized phenotyping. Nature Methods 2, 403–404 (2005).

    CAS  Article  PubMed  Google Scholar 

  21. Hancock, J. M. & Gates, H. Understanding mammalian genetic systems: the challenge of phenotyping in the mouse. PLoS Genet. 2, e118 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Davisson, M. FIMRe: Federation of International Mouse Resources: global networking of resource centers. Mamm. Genome 17, 363–364 (2006).

    Article  PubMed  Google Scholar 

  23. Lieschke, G. J. & Currie, P. D. Animal models of human disease: zebrafish swim into view. Nature Rev. Genet. 8, 353–367 (2007).

    CAS  Article  PubMed  Google Scholar 

  24. Hubner, N. et al. Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease. Nature Genet. 37, 243–253 (2005).

    CAS  Article  PubMed  Google Scholar 

  25. Complex Trait Consortium. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nature 26, 1133–1137 (2004).

  26. Lage, K. et al. A human phenome–interactome network of protein complexes implicated in genetic disorders. Nature Biotechnol. 25, 309–316 (2007).

    CAS  Article  Google Scholar 

  27. Goh, K. I. et al. The human disease network. Proc. Natl Acad. Sci. USA 104, 8685–8690 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Taussig, M. J. et al. ProteomeBinders: planning a European resource of affinity reagents for analysis of the human proteome. Nature Methods 4, 13–17 (2007).

    CAS  Article  PubMed  Google Scholar 

  29. Rubio-Aliaga, I. et al. A genetic screen for modifiers of the delta1-dependent notch signaling function in the mouse. Genetics 175, 1451–1463 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Hardisty-Hughes, R. E. et al. A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse. Hum. Mol. Genet. 15, 3273–3279 (2006).

    CAS  Article  PubMed  Google Scholar 

  31. Segade, F. et al. Association of the FBXO11 gene with chronic otitis media with effusion and recurrent otitis media: the Minnesota COME/ROM Family Study. Arch. Otolaryngol. Head Neck Surg. 132, 729–733 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Parkinson, N. et al. Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media. PLoS Genet. 2, e149 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  33. van Rooij, E., Sutherland, L. B., Qi, X., Richardson, J. A., Hill, J., Olson, E. N. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316, 575–579 (2007).

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rosenthal, N., Brown, S. The mouse ascending: perspectives for human-disease models. Nat Cell Biol 9, 993–999 (2007).

Download citation

  • Issue Date:

  • DOI:

Further reading


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