Ccs6^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Ccs6^C3H/HeJ
• Name: colon cancer susceptibility 6; C3H/HeJ
• MGI ID: MGI:6330765
• QTL: Ccs6 Location: Chr6:40776934-40776934 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:242437

Inbred strains of mice differ in susceptibility to colitis-associated colorectal cancer (CA-CRC). The authors tested 10 inbred strains of mice (129S1/SvImJ, A/J, AKR/J, BALB/cByJ, C3H/HeJ, C57Bl/6J, CBA/J, DBA/2J, FVB/NJ, and NOD/ShiLtJ) for their response to azoxymethane/dextran sulfate sodium-induced CA-CRC and identified a bimodal inter-strain distribution pattern when tumor multiplicity was used as a phenotypic marker of susceptibility. The FVB/NJ strain was particularly susceptible showing a higher tumor burden than any other susceptible strains (12.5-week post-treatment initiation). FVB/NJ hyper-susceptibility was detected as early as 8-week post-treatment initiation with FVB/NJ mice developing 5.5-fold more tumors than susceptible A/J or resistant C57BL/6J control mice.

The authors generated (FVB/NJ x C3H/HeJ)F1 mice by mating a FVB/NJ female with a C3H/HeJ male, and the resulting F1 progeny mice were inter-crossed to generate (FVB/NJ x C3H/HeJ)F2 mice.

A total of 82 (FVB/NJ x C3H/HeJ)F2 samples (36 most susceptible and 46 most resistant mice) along with 1 FVB/NJ and 1 C3H/HeJ mouse were genotyped for 1449 SNPs on the Illumina Medium Density Linkage Analysis panel at The Centre for Applied Genomics (TCAG) at the Hospital for Sick Children (Toronto, ON, Canada). Of the SNPs tested on the panel, 596 markers were found to be polymorphic between C3H/HeJ and FVB/NJ. QTL linkage analysis of 82 (FVB/NJ x C3H/HeJ)F2 mice (36 most susceptible and 46 most resistant mice) using susceptibility as a binary trait was conducted using R/qtl software and the EM maximum likelihood algorithm.

Linkage analysis identified one novel susceptibility locus:

Ccs6 (colon cancer susceptibility 6) maps to Chr6 with a peak LOD score of 3.86 at 40.8 Mb. The LOD score increased to 5.4 (peak marker rs13478727, 43.8 Mbp) when gender was used as a covariate. The Ccs6 locus regulates CA-CRC susceptibility in a recessive manner, and mice homozygous for FVB/NJ alleles at this locus had increased tumor multiplicity compared to homozygous C3H/HeJ mice.

References

• Original: J:242437 Van Der Kraak L, et al., Mapping hyper-susceptibility to colitis-associated colorectal cancer in FVB/NJ mice. Mamm Genome. 2016 Jun;27(5-6):213-24
• All: 1 reference(s)