title: The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis.
abstract: 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.
  
  
  RESULTS
  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(-/-) phenotype 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.
authors: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy. ida.casorelli@ospedalesantandrea.it
authors: Ida
authors: I
authors: Casorelli
authors: Tania
authors: T
authors: Pannellini
authors: Gabriele
authors: G
authors: De Luca
authors: Paolo
authors: P
authors: Degan
authors: Federica
authors: F
authors: Chiera
authors: Ivano
authors: I
authors: Iavarone
authors: Alessandro
authors: A
authors: Giuliani
authors: Alessia
authors: A
authors: Butera
authors: Monica
authors: M
authors: Boirivant
authors: Piero
authors: P
authors: Musiani
authors: Margherita
authors: M
authors: Bignami
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D051379:Mice; D053842:Microsatellite Instability / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D004247:DNA; D016264:Dextran Sulfate; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase