Experiment
To identify genetic determinants of skin cancer susceptibility and carcinoma development, a large backcross population of FVB/NJcl x (FVB/NJcl x MSM/Ms) F1 mice were subjected to DMBA/TPA-induced skin carcinogenesis. MSM/Ms mice are more resistant to chemically induced skin tumor development than the highly susceptible FVB/N strain.
(FVB/NJcl x MSM/Ms) male mice were backcrossed with female FVB/NJcl mice generating 121 F1 Tpr53 homozygous mice, p53+/+. Tpr53 deficient male mice (FVB/NJcl x MSM.Cg-Trp53tm1Sia/+) were backcrossed to female FVB/NJcl mice generating 107 Tpr53 heterozygous F1 backcross mice, p53+/-. Mice were genotyped using PCR assays.
Tumor development was monitored for a period of 40 weeks; the number of papillomas at 20 weeks as well as the presence of carcinomas at 40 weeks was documented. In addition papillomas were categorized into three groups based on diameter size, <2mm, 2-6mm and >6mm. All mice were genotyped using 107 SNP markers distributed evenly over the genome.
In the analysis of combined results from both crosses, 121 FVB/NJcl x (FVB/NJcl x MSM/Ms)F1 mice and 107 (FVB/NJcl x (FVB/NJcl x MSM.Cg-Tpr53tmSia1/+)F1, the following significant QTL was detected on Chromosome 6.
QTL Stmm4, skin tumor modifier of MSM 4, a measure of the total number of papillomas found, LOD=4.355 was mapped to 36.0 cM.
QTL Stmm4a, skin tumor modifier of MSM 4a, a measure of the number of papillomas between 2 and 6mm, LOD=3.78 also mapped to 36.0 cM on Chromosome 6.