International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

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E20 Evaluation of the Influence of Strain Background on the Development of Adenomas in Apc Min/+ Mice

Revati Koratkar, Karen Silverman, Arthur M. Buchberg, and Linda D. Siracusa. Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107-5541, USA

Genetic background strongly influences development of adenomas in the Multiple intestinal neoplasia (Min) model in mice. C57BL/6J (B6) mice heterozygous for a mutation in the Apc gene develop ~100 adenomas along their small intestines, and die due to anemia and/or intestinal obstruction within the first six months of life. In comparison, mice heterozygous for the same ApcMin mutation on a hybrid C57BL/6J X C3H/HeJ (C3H) background show significantly reduced tumor numbers. Modifier of Min1 (Mom1), a locus on the distal region of mouse chromosome 4, can influence tumor burden by approximately 50%. Secretory phospholipase (Pla2g2a) remains the most likely candidate for the Mom1 locus. We have now constructed reciprocal congenic lines, with susceptible and resistant B6 and C3H strains respectively, by a breeding and selection method. These congenic lines were generated such that the susceptible strain (B6) carries the resistant Pla2g2a+ allele, and the resistant strain (C3H) carries the susceptible Pla2g2a- allele. Progeny of each congenic line mated with B6 ApcMin/+ mice were aged and screened for intestinal adenomas. The results indicate that the C3H strain carries additional resistant alleles which significantly reduce tumor burden by approximately 4-fold. Quantitative trait loci analyses should facilitate the localization of chromosomal regions harboring these modifier genes and ultimately lead to their identification and characterization.


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