Analysis of reciprocal congenic lines reveals the C3H/HeJ genome to be highly resistant to ApcMin intestinal tumorigenesis.

Abstract Genetic background affects polyp development in the Multiple intestinal neoplasia ( Apc Min ) mouse model. The Modifier of Min 1 ( Mom1 ) locus accounts for ~50% of the variation in polyp multiplicity. We generated reciprocal congenic lines, such that the recipient C57BL/6J (B6) strain carries a donor C3H/HeJ (C3H) Mom1 allele, and the recipient C3H strain carries a donor B6 Mom1 allele. Hybrid progeny from congenic females mated to B6 Apc Min/+ males were analyzed. A single C3H Mom1 locus on the B6 background reduced small intestinal polyp numbers by 50% and colon polyp incidence by 66% compared to their susceptible B6 Mom1 S/S Apc Min/+ siblings. These findings show that the C3H genome contains a resistant Mom1 R locus. The reciprocal congenic line, which carries the susceptible B6 Mom1 S locus on the C3H background, reduced small intestinal polyp numbers by 80% and colon polyp incidence by 95% compared to B6 Mom1 S/S Apc Min/+ mice. These data demonstrate that unidentified modifiers in the C3H strain can suppress intestinal polyp multiplicity in Apc Min/+ mice, and act in the absence of a resistant Mom1 R locus.