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Mlh1 deficiency enhances several phenotypes of ApcMin/+ mice

Oncogene volume 19, pages 2774–2779 (2000)Cite this article

Abstract

Defects in APC and DNA mismatch repair genes are associated with a strong predisposition to colon cancer in humans, and numerous mouse strains with mutations in these genes have been generated. In this report we describe the phenotype of Min/+ Mlh1−/− mice. We find that these doubly mutant mice develop more than three times the number of intestinal adenomas compared to Min/+ Mlh1+/+ or +/− mice but that these tumors do not show advanced progression in terms of tumor size or histological appearance. Full length Apc protein was not detected in the tumor cells from Min/+ Mlh1−/− mice. Molecular analyses indicated that in many tumors from Min/+ Mlh1−/− mice, Apc was inactivated by intragenic mutation. Mlh1 deficiency in Min/+ mice also led to an increase in cystic intestinal crypt multiplicity as well as enhancing desmoid tumorigenesis and epidermoid cyst development. Thus, Mlh1 deficiency influences the somatic events involved in the development of most of the phenotypes associated with the Min mutation.

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Acknowledgements

We thank Natalie Borenstein, Thomas Flath, Dana Olson, Cheri Pasch, and Jane Weeks for expert technical assistance; Carol Midgley for providing the Apc antibody; Henry Pitot for histological consultation; and Linda Clipson for help with preparing the manuscript. This work was supported by grants from the National Institutes of Health (CA07075 to the McArdle Laboratory, CA58085 and CA63677 to WF Dove and GM32741-18 to RM Liskay). KM Haigis was supported by NIH predoctoral training grant 5T32GM07133. This is publication No. 3560 from the Laboratory of Genetics.

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  1. McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin Medical School, Madison, 53706, Wisconsin, WI, USA

    Alex R Shoemaker, Kevin M Haigis & William F Dove

  2. Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, 97201, Oregon, OR, USA

    Sean M Baker, Sandy Dudley & R Michael Liskay

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Shoemaker, A., Haigis, K., Baker, S. et al. Mlh1 deficiency enhances several phenotypes of ApcMin/+ mice. Oncogene 19, 2774–2779 (2000). https://doi.org/10.1038/sj.onc.1203574

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