Mom12^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Mom12^C57BL/6J
• Name: Modifier of Min 12; C57BL/6J
• MGI ID: MGI:5775813
• QTL: Mom12 Location: Chr6:50872261-50872400 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

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

J:201191

Data suggest that CAV1 may act as a tummor suppressor gene in the intestinal tract. In this study, the authors sought to analyze the effect of loss of Cav1 gene expression on Apc^Min mediated tumorigenesis.

Female B6J.Cg-Cav1^tm1Mls/Cav1^tm1Mls (B6-Cav1^-/-) mice were mated to male C57BL/6J-Apc^Min/+/J (B6-Apc^Min/+) mice. The F1 offspring were backcrossed to the B6-Cav1^-/- parental strain. N2 offspring were then intercrossed to create a colony of mice carrying the Apc^Min mutation in combination with all 3 potential Cav1 genotypes, Cav1^-/Cav1^-, Cav1^-/+ and Cav1^+/+.

Increased polyp multiplicity was observed in the offspring of the (B6-Cav1^-/-) x (B6-Apc^Min/+) cross compared to (B6-Apc^Min/+) controls. The genotype of the Cav1 locus, however, did not correlate with polyp multiplicity, implying the presence of other modifier loci segregating within the colony. Satistical analysis indicated that the increased tumorigenesis observed in the colony was not the result of decreased Cav1 expression.

The Cav1^-/Cav1^- line was generated using the WW6 ES cell line, which is derived from a cross between 3 different inbred strains: 129X1/SvJ, C57BL/6J and SJL. Mice carrying the knockout allele (Cav1) were then crossed to B6 mice for 8 generations. At N8, app 25% of the genomic DNA linked to Cav1 is theoretically derived from the donor WW6 ES line. Consequently the Cav1^-/Cav1^- mice may retain some of this non-B6 DNA.

The (B6-Cav1^-/-) x B6-Apc^Min/+) colony was genotyped for SSLP markers across the length of Chromosome 6. 129X1 genomic DNA was observed at 4 markers distal to the Cav1 locus: D6Mit205, D6Mit268, D6Mit207 and D6Mit33; only B6 DNA was found at Marker D6Mit138 (proximal to Cav1) and marker D6Mit316 (distal to D6Mit33); the genotyping data defined a 51 Mb congenic region on Chr 6 that carried residual 129X1 genomic DNA. To determine if a modifier gene was present in the congenic region the distribution of polyp multiplicity data in the colony was examined based on the genotypes at 5 loci within the congenic region.

Mice in the 129/B6 genotype at the D6Mit33 marker had a distribution with a single peak centered between the two B6/B6 groups. The single 129/B6 group was significantly different than the low and the high B6/B6 groups in both male an female mice.

Authors offer the most likely hypothesis explaining these 3 phenotypic groups is the existance of two dominant modifier loci segregating in the (B6-Cav1^-/-) x B6-Apc^Min/+) colony.

One dominant modifier is referred to as Mom12, modifier of Min 12, and is linked to the 129X1 allele at D6Mit33 on Chr 6. The Mom12 susceptible allele results in an increase in polyp multiplicity compared to Apc^Min/+ controls.

A second dominant locus, unlinked to the congenic region, is referred to as Mom13, modifier of Min 13. In the absence of the Mom12 susceptible allele, the Mom13 susceptible allele results in increased polyp multiplicity. The Mom13 locus may be the result of a spontaneous mutation or residual 129X1 DNA.

References

• Original: J:201191 Crist RC, et al., Identification of Mom12 and Mom13, two novel modifier loci of Apc (Min) -mediated intestinal tumorigenesis. Cell Cycle. 2011 Apr 1;10(7):1092-9
• All: 1 reference(s)