title: Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.
abstract: The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.
authors.affiliation: Department of Food Safety and Infection Biology, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Sødring
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Gjermund
authors.initials: G
authors.lastname: Gunnes
authors.affiliation: Department of Food Safety and Infection Biology, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Paulsen
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: A/J Min/+ mouse; carcinoma; colorectal cancer; intestinal tumorigenesis