Winnie- APCMin/+ Mice: A Spontaneous Model of Colitis-Associated Colorectal Cancer Combining Genetics and Inflammation

Int J Mol Sci. 2020 Apr 23;21(8):2972. doi: 10.3390/ijms21082972.

Abstract

(1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with ApcMin/+ mice. (3) Results: The resulting Winnie-ApcMin/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie-ApcMin/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie-ApcMin/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.

Keywords: Aberrant Crypt Foci; colorectal cancer; inflammation; murine model.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biopsy
  • Cell Proliferation
  • Colitis-Associated Neoplasms / etiology*
  • Cytoskeleton
  • Disease Models, Animal
  • Disease Progression
  • Disease Susceptibility*
  • Genes, APC*
  • Genetic Predisposition to Disease
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Mice
  • Neoplasm Grading