The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis

Gastroenterology. 2001 Dec;121(6):1407-16. doi: 10.1053/gast.2001.29609.


Background & aims: Differences in genetic background may play a role in the development of ulcerative colitis (UC)-related neoplasia. Loss of heterozygosity (LOH) of APC has been reported in human UC-associated neoplasia. To investigate the role of genetic differences in UC-associated neoplasia, we compared differences in dextran sodium sulfate (DSS) colitis-associated neoplasia between wild-type C57BL/6J mice (WT-DSS) and C57BL/6J mice with a germline mutation in Apc (Min-DSS).

Methods: DSS colitis was induced in female wild-type and Min mice. Age- and sex-matched non-DSS-treated Mins were also studied. Animals were sacrificed after 1 and 2 cycles of DSS. The cecums and large intestines were studied for numbers of dysplasias/cancers. Dysplasias were studied for LOH of Apc.

Results: No WT-DSS, 100% of Min-DSS, and 50% of non-DSS-treated Mins had dysplasia. The mean numbers of lesions per mouse were 0 (WT-DSS), 15.6 and 29.3 (1 and 2 cycles Min-DSS, respectively), 1.2 and 1.9 (age-matched control Min, 1 and 2 cycle equivalents, respectively; P < 0.0002, Min-DSS vs. WT-DSS and non-DSS-treated Min; P = 0.03, Min-DSS 2 cycle vs. Min-DSS 1 cycle). Cancers were seen in 0%, 22%, and 40% of non-DSS Min, Min-DSS-1 cycle, and Min-DSS-2 cycle animals, respectively. LOH of Apc was observed in 90.6% of dysplasias and 6% of nondysplastic mucosa.

Conclusions: A germline mutation in Apc contributes significantly to the development of colitis-associated neoplasia. Colitis markedly accelerates the development of dysplasia and cancer in the Min mouse. Dysplasia in Min-DSS occurs through LOH of Apc.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / epidemiology
  • Adenoma / genetics
  • Adenoma / pathology
  • Animals
  • Colitis / chemically induced*
  • Colitis / genetics*
  • Colitis / pathology
  • Colonic Diseases / epidemiology
  • Colonic Diseases / genetics*
  • Colonic Diseases / pathology
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Dextran Sulfate*
  • Female
  • Genes, APC*
  • Germ-Line Mutation / physiology*
  • Incidence
  • Loss of Heterozygosity
  • Mice
  • Mice, Inbred C57BL / genetics
  • Ulcer / genetics
  • Ulcer / pathology


  • Dextran Sulfate