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.

  • Commentary
  • Published:

New tools for defining the 'genetic background' of inbred mouse strains

There is general appreciation that 'genetic background effects' can profoundly affect the immune phenotypes of congenic, transgenic and knockout mice. We suggest that attributing phenotypes to genetic background effects is outmoded and that new databases containing single-nucleotide polymorphisms obtained with a group of inbred mouse strains can be used to define the flanking DNA of nearly all mouse genes.

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

Access options

Buy this article

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

Figure 1: The flanking-gene problem, demonstrated by hypothetical congenic, transgenic and knockout intervals crossed onto the NOD background.
Figure 2: SNP maps generated from the T1Dbase website (http://dil.t1dbase.org/page/PerlegenSNPs).

References

  1. Wakeland, E., Morel, L., Achey, K., Yui, M. & Longmate, J. Speed congenics: a classic technique in the fast lane (relatively speaking). Immunol. Today 18, 472–477 (1997).

    Article  CAS  Google Scholar 

  2. Wicker, L.S., Todd, J.A. & Peterson, L.B. Genetic control of autoimmune diabetes in the NOD mouse. Annu. Rev. Immunol. 13, 179–200 (1995).

    Article  CAS  Google Scholar 

  3. Petes, T.D. Meiotic recombination hot spots and cold spots. Nat. Rev. Genet. 2, 360–369 (2001).

    Article  CAS  Google Scholar 

  4. Simpson, E.M. et al. Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat. Genet. 16, 19–27 (1997).

    Article  CAS  Google Scholar 

  5. Leiter, E.H. Mice with targeted gene disruptions or gene insertions for diabetes research: problems, pitfalls, and potential solutions. Diabetologia 45, 296–308 (2002).

    Article  CAS  Google Scholar 

  6. Flint, J., Valdar, W., Shifman, S. & Mott, R. Strategies for mapping and cloning quantitative trait genes in rodents. Nat. Rev. Genet. 6, 271–286 (2005).

    Article  CAS  Google Scholar 

  7. Wolfer, D.P., Crusio, W.E. & Lipp, H.P. Knockout mice: simple solutions to the problems of genetic background and flanking genes. Trends Neurosci. 25, 336–340 (2002).

    Article  CAS  Google Scholar 

  8. Wang, B. et al. Interferon-γ impacts at multiple points during the progression of autoimmune diabetes. Proc. Natl. Acad. Sci. USA 94, 13844–13849 (1997).

    Article  CAS  Google Scholar 

  9. Kanagawa, O., Xu, G., Tevaarwerk, A. & Vaupel, B.A. Protection of nonobese diabetic mice from diabetes by gene(s) closely linked to IFN-γ receptor loci. J. Immunol. 164, 3919–3923 (2000).

    Article  CAS  Google Scholar 

  10. Hubbard, T.J.P. et al. Ensembl 2007. Nucleic Acids Res. D610–D617 (2007).

  11. Witmer, P.D. et al. The development of a highly informative mouse simple sequence length polymorphism (SSLP) marker set and construction of a mouse family tree using parsimony analysis. Genome Res. 13, 485–491 (2003).

    Article  CAS  Google Scholar 

  12. Hulbert, E.M. et al. T1DBase: integration and presentation of complex data for type 1 diabetes research. Nucleic Acids Res. 35, D742–D746 (2007).

    Article  CAS  Google Scholar 

  13. Lyons, P.A. et al. The NOD Idd9 genetic interval influences the pathogenicity of insulitis and contains molecular variants of Cd30, Tnfr2, and Cd137. Immunity 13, 107–115 (2000).

    Article  CAS  Google Scholar 

  14. Cannons, J.L. et al. Genetic and functional association of the immune signaling molecule 4–1BB (CD137/TNFRSF9) with type 1 diabetes. J. Autoimmun. 25, 13–20 (2005).

    Article  CAS  Google Scholar 

  15. Irie, J., Wu, Y., Sass, D.A. & Ridgway, W.M. Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region. Immunogenetics 58, 9–14 (2006).

    Article  CAS  Google Scholar 

  16. Cuppen, E. Haplotype-based genetics in mice and rats. Trends Genet. 21, 318–322 (2005).

    Article  CAS  Google Scholar 

  17. Wiltshire, T. et al. Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse. Proc. Natl. Acad. Sci. USA 100, 3380–3385 (2003).

    Article  CAS  Google Scholar 

  18. Edwards, S.V., Chesnut, K., Satta, Y. & Wakeland, E.K. Ancestral polymorphism of Mhc class II genes in mice: implications for balancing selection and the mammalian molecular clock. Genetics 146, 655–668 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Yamanouchi, J. et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat. Genet. 39, 329–337 (2007).

    Article  CAS  Google Scholar 

  20. Yalcin, B. et al. Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice. Proc. Natl. Acad. Sci. USA 101, 9734–9739 (2004).

    Article  CAS  Google Scholar 

  21. Brook, F.A. et al. The derivation of highly germline-competent embryonic stem cells containing NOD-derived genome. Diabetes 52, 205–208 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by the Juvenile Diabetes Research Foundation (L.S.W.), the Wellcome Trust (L.S.W.), the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (W.M.R.) and the Autoimmunity Center of Excellence program (W.M.R.).

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ridgway, W., Healy, B., Smink, L. et al. New tools for defining the 'genetic background' of inbred mouse strains. Nat Immunol 8, 669–673 (2007). https://doi.org/10.1038/ni0707-669

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni0707-669

This article is cited by

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