Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair

Tomas A. Prolla, Sean M. Baker, Allie C. Harris, Jen Lan Tsao, Xiang Yao, C. Eric Bronner, Binhai Zheng, Melissa Gordon, Jeffrey Reneker, Norman Arnheim, Darryl Shibata, Allan Bradley, R. Michael Liskay

Research output: Contribution to journalArticlepeer-review

306 Scopus citations


Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5). An important role for DNA replication errors in colorectal tumorigenesis has been suggested by the finding of frequent alterations in the length of specific mononucleotide tracts within genes controlling cell growth, including TGF-β receptor type II (ref. 6), BAX (ref. 7) and APC (ref. 8). A broader role for MMR deficiency in human tumorigenesis is implicated by microsatellite instability in a fraction of sporadic tumours, including gastric, endometrial and colorectal malignancies. To better define the role of individual MMR genes in cancer susceptibility and MMR functions, we have generated mice deficient for the murine homologues of the human genes MLH1, PMS1 and PMS2. Surprisingly, we find that these mice show different tumour susceptibilities, most notably, to intestinal adenomas and adenocarcinomas, and different mutational spectra. Our results suggest that a general increase in replication errors may not be sufficient for intestinal tumour formation and that these genes share overlapping, but not identical functions.

Original languageEnglish (US)
Pages (from-to)276-279
Number of pages4
JournalNature genetics
Issue number3
StatePublished - 1998

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair'. Together they form a unique fingerprint.

Cite this