Analysis of reciprocal congenic lines reveals the C3H/HeJ genome to be highly resistant to ApcMin intestinal tumorigenesis.
Genetic background affects polyp development in the Multiple intestinal neoplasia (Apc(Min)) mouse model. The Modifier of Min 1 (Mom1) locus accounts for approximately 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.
Koratkar
Revati
R
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
Silverman
Karen A
KA
Pequignot
Ed
E
Hauck
Walter W
WW
Buchberg
Arthur M
AM
Siracusa
Linda D
LD
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D033481:Chromosomes, Mammalian / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC; D016678:Genome; D054501:Group II Phospholipases A2; D007417:Intestinal Polyps / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D010641:Phenotype; D010741:Phospholipases A / Q000235:genetics*
D010741:Phospholipases A; D054501:Group II Phospholipases A2