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

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 adenocarcinomes ( 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. © 2005 Wiley‐Liss, Inc.