Originally published as Genetics Published Articles Ahead of Print on April 15, 2007.

Genetics, Vol. 176, 1237-1244, June 2007, Copyright © 2007
doi:10.1534/genetics.107.071217

Identification of Mom7, a Novel Modifier of Apc^Min/+ on Mouse Chromosome 18

Lawrence N. Kwong^*, Alexandra Shedlovsky^*, Bryan S. Biehl^*, Linda Clipson^*, Cheri A. Pasch^* and William F. Dove^*,,1

^* McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706

¹ Corresponding author: McArdle Laboratory for Cancer Research, 1400 University Ave., Madison, WI 53706.
E-mail: dove{at}oncology.wisc.edu

The Apc^Min mouse model of colorectal cancer provides a discrete, quantitative measurement of tumor multiplicity, allowing for robust quantitative trait locus analysis. This advantage has previously been used to uncover polymorphic modifiers of the Min phenotype: Mom1, which is partly explained by Pla2g2a; Mom2, a spontaneous mutant modifier; and Mom3, which was discovered in an outbred cross. Here, we describe the localization of a novel modifier, Mom7, to the pericentromeric region of chromosome 18. Mom7 was mapped in crosses involving four inbred strains: C57BL/6J (B6), BTBR/Pas (BTBR), AKR/J (AKR), and A/J. There are at least two distinct alleles of Mom7: the recessive, enhancing BTBR, AKR, and A/J alleles and the dominant, suppressive B6 allele. Homozygosity for the enhancing alleles increases tumor number by approximately threefold in the small intestine on both inbred and F₁ backgrounds. Congenic line analysis has narrowed the Mom7 region to within 7.4 Mb of the centromere, 28 Mb proximal to Apc. Analysis of SNP data from various genotyping projects suggests that the region could be as small as 4.4 Mb and that there may be five or more alleles of Mom7 segregating among the many strains of inbred mice. This has implications for experiments involving Apc^Min and comparisons between different or mixed genetic backgrounds.

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