Mom14^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Mom14^C3H/HeJ
• Name: modifier of Min 14; C3H/HeJ
• MGI ID: MGI:5776001
• QTL: Mom14 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:188401

In this study female mice from BXH RI lines were crossed to C57BL/6J-Apc^Min/J males to produce F1 hybrid progeny. Five BXH RI lines (BXH2, BXH4, BXH8, and BXH14 and BXH22 and one BXH RC line, BcH1 were tested for their susceptibility or resistance to intestinal tumorigenesis. The progenitor inbred strains for the BXH RI lines were C57BL/6J (B6) and C3H/HeJ (C3H). The Apc^Min/+ offspring from each group, hereafter referred to as BXH# F1,

were aged to 110-130 days and scored for adenomas throughout the small intestine and colon.

The BXH14 F1 group was unique in that it exhibited the lowest small intestinal polyp numbers of all lines tested; it also had the lowest average of colon polyps and incidence of all lines tested. Compared with the more susceptible lines the BXH14 line also developed fewer polyps in each region of the small intestine and colon.

A SNP panel was used to genotype 39 BXH14 mice from the N2 and N3 backcross generations across the genome to identify C3H/hHeJ alleles that acted to lower polyp numbers. Five loci were identified; in each case the SNPs that reached the highest significance were C3H alleles. Because the SNPs were flanked by C3H alleles, the low polyp phenotype most likely originated from the C3H genome.

Mom14, modifier of Min 14, p<0.05 was identified on Chromosome 1 mapping between 139-174 Mb on NCBI m37.

Mom15, modifier of Min 15, p<0.05 was identified on the proximal region of Chromosome 2 mapping between 105-126 Mb on NCBI m37.

Mom16, modifier of Min 16, p<0.05 mapped to the distal region of Chromosome 2 between 131 Mbs and the telomere on NCBI m37.

Mom17, modifier of Min 17, p<0.05 mapped to Chromosome 10 between 36-96 Mbs on NCBI m37.

Mom18, modifier of Min 18, p<0.05 mapped to Chromosome 18 between 12-34 Mbs also on NCBI m37.

When each of the five Mom# QTL were considered individually the, average polyp numbers were decreased by 39% for Mom14, 51% for Mom15, 46% for Mom16, 39% for Mom17 and 52% for Mom18 in the heterozygous B6/C3H group compared with the B6/B6 group. Regardless of the combination, inheritance of four or more C3H alleles at the Mom14-18 loci resulted in a 61-72% decrease in the polyp number.

In an analysis of gene-to-gene interactions the highest scoring networks were generated when genes located within all five Mom(14-18) regions were evaluated together; indicating that there are multiple possibilities by which gene-gene interactions could affect polyposis.

References

• Original: J:188401 Nnadi SC, et al., Identification of five novel modifier loci of Apc(Min) harbored in the BXH14 recombinant inbred strain. Carcinogenesis. 2012 Aug;33(8):1589-97
• All: 1 reference(s)