Target-Selected ENU Mutagenesis to Develop Cancer Models in the Rat

  • Bart M. G. Smits
  • Edwin Cuppen
  • Michael N. Gould


Over the last decade, the laboratory rat has matured as a genetic model organism. One of the most valuable additions to its genetic toolbox is the ability to inactivate genes of interest using N-ethyl-N-nitrosourea mutagenesis-based reverse genetics. The Gould lab (McArdle Laboratory for Cancer Research, University of Wisconsin – Madison, USA) and the Cuppen lab (Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands) have developed this technology for a variety of rat strains. This resulted in the identification and characterization of a number of novel rat models, including novel models for breast and colon cancer. This chapter describes the establishment of the rat knockout technology and the characterization of the rat knockout models for the tumor suppressor genes APC, BRCA1, BRCA2, and MSH6.


Quantitative Trait Locus Adenomatous Polyposis Coli Lynch Syndrome Premature Stop Codon Sleep Beauty 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are grateful to Dr. James Amos-Landgraf (University of Wisconsin – Madison) for kindly providing an endoscopic picture of a rat colonic adenoma marked with a tattoo. We are grateful to Mr. Ruben van Boxtel (Hubrecht Institute – Utrecht, Netherlands) for critically reading the manuscript. BMGS has been supported by a Postdoctoral Award from the Era of Hope Breast Cancer Research Program of the Department of Defense.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Bart M. G. Smits
    • 1
  • Edwin Cuppen
    • 2
  • Michael N. Gould
    • 1
  1. 1.McArdle Laboratory for Cancer Research, Department of OncologyUniversity of Wisconsin – MadisonMadisonUSA
  2. 2.Hubrecht Institute for Developmental Biology and Stem Cell ResearchSection Functional Genomics and BioinformaticsUtrechtThe Netherlands

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