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.

Genome-wide, large-scale production of mutant mice by ENU mutagenesis


In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations1. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper2, leads to a significant increase in the number of mouse models3 available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Structure of the ENU–mouse-mutagenesis research centre.
Figure 2: Mutants identified in the clinical chemical screen.
Figure 3: Mutants identified in the immunology screen.
Figure 4: Forelimbs of mouse mutant ALI4 (for abnormal limb 4), showing abnormal growth and nail colour caused by disturbance in the matrix of the nail bed and hyper-parakeratosis.


  1. Hrabé de Angelis, M. & Balling, R. Large scale ENU screens in the mouse. Genetics meets genomics. Mutat. Res. 400, 25–32 (1998).

    Article  Google Scholar 

  2. Nolan, P.M. et al. A systematic, genome-wide, phenotype-driven mutagenesis program for gene function studies in the mouse. Nature Genet. 25, 440–443 (2000).

    Article  CAS  Google Scholar 

  3. Brown, S. & Peters, J. Combining mutagenesis and genomics in the mouse—closing the phenotype gap. Trends Genet. 12, 433–435 (1996).

    Article  CAS  Google Scholar 

  4. Graw, J. et al. Mutation in the bA3/A1-crystallin encoding gene Cryba1 causes a dominant cataract in the mouse. Genomics 62, 67–73 (1999)

    Article  CAS  Google Scholar 

  5. Marschall, S. & Hrabé de Angelis, M. Cryopreservation of mouse spermatozoa–double your mouse space. Trends Genet. 15, 128–131 (1999).

    Article  CAS  Google Scholar 

  6. Marschall, S., Huffstadt, U., Balling, R. & Hrabé de Angelis, M. Reliable recovery of inbred mouse lines using cryopreserved spermatozoa. Mamm. Genome 10, 773–776 (1999).

    Article  CAS  Google Scholar 

  7. Whyte, M.P., Teitelbaum, S.L., Murphy, W.A., Bergfeld, M.A. & Avioli, L.V. Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature. Medicine 58, 329–347 (1979).

    Article  CAS  Google Scholar 

  8. Spickett, G.P. et al. Common variable immunodeficiency: how many diseases? Immunol. Today 18, 325–328 (1997).

    Article  CAS  Google Scholar 

  9. Ahearn, J.M. et al. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity 4, 251–262 (1996).

    Article  CAS  Google Scholar 

  10. Molina, H. et al. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc. Natl Acad. Sci. USA 93, 3357–3361 (1996).

    Article  CAS  Google Scholar 

  11. Russell, W.L. et al. Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc. Natl Acad. Sci. USA 76, 5918–5922 (1979).

    Google Scholar 

  12. Justice, M.J., Noveroske, J.K., Weber, J.S., Zheng, B. & Bradley, A. Mouse ENU mutagenesis. Hum. Mol. Genet. 8, 1955–1963 (1999).

    Article  CAS  Google Scholar 

  13. Nolan, P.M., Kampfhamer, D. & Bucan, M. Random mutagenesis screen for dominant behavioral mutations in mice. Methods 13, 379–395 (1997).

    Article  CAS  Google Scholar 

Download references


We thank A. Servatius, S. Prettin, G. Bergter, N. Hirsch, A. Mayer, S. Manz, S. Hoffmann, F. Golla, B. Beneckenstein, K. Lobenwein, A. Wolf and D. Kreitz for technical assistance; C. Schindewolf for comments and revision of the manuscript; and H. Wagner for support. Part of this project was supported by grants from the German Human Genome Project to R.B., E.W. and M.H.d.A. (01KW9610/1), and to K.P., J.R. and H.B. (01KW9636).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Martin Hrabé de Angelis.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

de Angelis, M., Flaswinkel, H., Fuchs, H. et al. Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25, 444–447 (2000).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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