Spontaneous Aberrant Crypt Foci in Apc1638N Mice with a Mutant Apc Allele

The Apc1638N /+ mouse has a chain-terminating mutation in one allele of the adenomatous polyposis coli ( Apc ) gene that is similar to most mutations observed in the human familial adenomatous polyposis syndrome. Aberrant crypt foci (ACF), the earliest identified neoplastic lesions in the colon, are morphologically abnormal structures that are identifiedmicroscopically in the grossly normal colonic mucosas of rodents treated with colon carcinogens and of human patients. The colons and cecums of 62 Apc1638N /+ mice were evaluated for the spontaneous occurrence of ACF and tumors. Both male and female mice were killed at different times between 5 and 28 weeks of age. Wild-type littermates, ie, Apc +/+ mice, at 22 to 26 weeks of age served as controls. ACF were identified in 97% of the Apc1638N /+ mice starting at 5 weeks of age and not in any wild-type littermates. Although the number of ACF increased with age ( P < 0.0001), the average number of crypts per focus of the ACF did not increase significantly. In addition, wild-type Apc protein was detected by immunohistochemistry in all 22 ACF evaluated. Together these data suggest that heterozygous loss of Apc may be sufficient to initiate ACF in these mice and that these mice may be suitable models to study the interaction of environmental factors with an inherited mutation of the Apc gene that is associated with colon cancer.