The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis

Ida Casorelli, Tania Pannellini, Gabriele de Luca, Paolo Degan, Federica Chiera, Ivano Iavarone, Alessandro Giuliani, Alessia Butera, Monica Boirivant, Piero Musiani, Margherita Bignami

Research output: Contribution to journalArticlepeer-review


Background: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh-/- mice to oxidative stress. Methodology/Principal Findings: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS). The Mutyh-/- phenotpe was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh-/- mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh-/- mice. Lymphoid hyperplasia and a significant reduction in Foxp3+ regulatory T cells were observed only in Mutyh-/- mice. Conclusions: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

Original languageEnglish
Article numbere12070
JournalPLoS One
Issue number8
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


Dive into the research topics of 'The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis'. Together they form a unique fingerprint.

Cite this