Generation of a unique strain of multiple intestinal neoplasia (Apc +/Min-FCCC) mice with significantly increased numbers of colorectal adenomas

Harry S. Cooper, Wen Chi L. Chang, Renata Coudry, Monique A. Gary, Lynette Everley, Cynthia S. Spittle, Hao Wang, Sam Litwin, Margie L. Clapper

Research output: Contribution to journalArticlepeer-review

Abstract

The relevance of the Apc+/Min mouse model in the study of human colorectal cancer remains uncertain due to the predominance of small intestinal adenomas and few, if any, colorectal adenomas. A new strain of Apc +/Min mice (Apc+/Min-FCCC) with significantly greater numbers of colorectal adenomas has been generated and characterized. Male C57BL/6J-Apc+/Min mice (the Jackson Laboratory, Bar Harbor, ME) were crossed with wild-type (Apc+/+) C57BL/ 6J females from an independent colony at this institution (offspring =Apc+/Min-FCCC) and 233 animals were evaluated over 20 generations. In order to determine the contribution of genetics to the enhanced colorectal adenoma phenotype, breeding pairs (Apc+/Min male × wild type female C57BL/6J) were purchased from the Jackson Laboratory and offspring (Apc+/Min-JAX) were maintained in our facility under identical conditions (n = 98). Animals were fed Purina Rodent chow (#5013) diet containing 5% fat. The entire intestinal tract was examined histopathologically in both strains. Both the Apc and Pla2g2a (candidate for Mom1) genes were sequenced and found to be identical for both the Apc+/Min-FCCC and Apc+/Min-JAX mouse strains. The multiplicity of colorectal adenomas in the Apc+/Min-FCCC mice was much higher than reported in the literature and significantly greater than the multiplicity of colorectal adenomas in Apc+/Min-JAX mice maintained in our facility (P = 0.01). Apc+/Min-FCCC had a significantly greater incidence of rectal prolapse (P = 0.02) and small intestinal adenocarcinomas (P = 0.001), and multiplicity of small intestinal adenocarcinomas (P = 0.001) compared to Apc+/Min-JAX mice. Male Apc+/Min-FCCC mice had significantly greater numbers of colorectal adenomas compared to female Apc+/Min-FCCC mice (P = 0.0002), as did male Apc+/Min-JAX mice vs. female Apc+/Min-JAX mice (P < 0.0001). These results allow us to conclude: (1) Apc+/Min-FCCC mice are unique in that they develop significantly greater numbers of colorectal adenomas and small intestinal cancers, and a significantly greater incidence of small intestinal cancers and rectal prolapse than Apc+/Min-JAX mice. (2) This study represents the first report of a significant gender difference in multiplicity of colorectal adenomas. (3) Differences between Apc +/Min-FCCC and Apc+/Min-JAX mice in currently undefined genetic modifiers may contribute to the enhanced colorectal phenotype. (4) The Apc+/Min-FCCC strain is highly suited for the investigation of colorectal neoplastic disease and chemoprevention studies.

Original languageEnglish (US)
Pages (from-to)31-41
Number of pages11
JournalMolecular Carcinogenesis
Volume44
Issue number1
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Animal models of colorectal neoplasia
  • Chemoprevention
  • Colorectal neoplasia
  • Colorectal polyps

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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