Cmmm^FVB/NJcl
QTL Variant Detail

Summary

• QTL variant: Cmmm^FVB/NJcl
• Name: carcinoma modifier of MSM; FVB/NJcl
• MGI ID: MGI:5795928
• QTL: Cmmm Location: Chr4:107590668-107590781 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: FVB/NJcl

Variant description

• Allele Type: QTL

Notes

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

J:193231

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-Trp53^tm1Sia/+) 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 FVB/NJcl x (FVB/NJcl x MSM/Ms) F1 backcrossed mice the following significant linkages were detected on Chromosome 4:

Stmm3a, skin tumor modifier of MSM 3a, a measure of the total number of papillomas >6mm in size at 20 weeks, LOD=5.358 at 44.7 cM. Approximately 73 percent of mice without tumors at this locus were heterozygous with FVB/MSM alleles.

Cmmm, carcinoma modifier of MSM, a measure of the total carcinoma at 40 weeks, LOD=4.049 at D4Mit43, 60.3 cM. Sixty nine percent of mice without carcinomas at this locus were heterozygous with FVB/MSM alleles. [Table 1.]

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-Tpr53/+)F1, the following significant QTL was detected on Chromosome 4.

Cmmm1, carcinoma modifier of MSM 1, a measure of the total carcinoma at week 40, LOD=4.410 at D4SNP27 (rs4137854), 59.5 cM.

QTL Stmm3, skin tumor modifier of MSM 3, a measure of the total number of papillomas >6mm in diameter at 20 weeks, LOD=6.992 mapped with peak marker D4SNP14 (rs31710891). To narrow the identified region, precise genotyping was performed with an additional 10 mircosatellite markers on 4. Stmm3 was mapped between D4Mit174 and D4Mit15 (an interval 10.7MB in size). [Fig 4B.]

Interestingly, 81.1 percent of the F1 backcrossed mice that developed papillomas larger than 6mm in size were homozygous for the FVB/N allele at D4SNP14 suggesting that the FVB/N allele at this locus confers strong susceptibility to increased papilloma growth.. [Table 1].

References

• Original: J:193231 Okumura K, et al., Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild-derived inbred mouse strain, MSM/Ms. Carcinogenesis. 2012 Nov;33(11):2260-8
• All: 1 reference(s)