The CAST/Ei strain confers significant protection against Apc(Min) intestinal polyps, independent of the resistant modifier of Min 1 (Mom1) locus.

Abstract

Intestinal adenoma development in Apc(Min) mice is influenced by genetic background. We generated a congenic line between the CAST and B6 inbred strains to study the effects of a resistant CAST background in the absence of a major modifier locus, Modifier of Min 1 (Mom1(R)). Progeny from a CAST.B6 Mom1(R/S) x B6 Apc(Min/+) intercross were 110 or 200 days of age and screened for intestinal polyps. There was a significant decrease (P < 0.0001) in polyp multiplicity and size in CASTB6F1 Mom1(R/S), Apc(Min/+) and CASTB6F1 Mom1(S/S), Apc(Min/+) progeny compared with B6 Mom1(S/S), Apc(Min/+) controls. A complete absence of colon polyps was observed in all mice heterozygous for the CAST background. These results demonstrate that the CAST strain carries dominant modifier loci, in addition to Mom1(R), that dramatically reduce polyp burden in the small intestine and eliminate polyp burden in the colon of Apc(Min) mice.