Skts12^{M. spretus}
QTL Variant Detail

Summary

• QTL variant: Skts12^{M. spretus}
• Name: skin tumor susceptibility 12; M. spretus
• MGI ID: MGI:2156470
• QTL: Skts12 Location: unknown Genetic Position: Chr6, cM position of peak correlated region/allele: 77.7 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: M. spretus

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to skin tumorigenesis compared to NIH/Ola. (J:59049)
• Inheritance: Dominant

Notes

Candidate Genes

J:85134

Several skin tumor susceptibility QTLs (Skts1-Skts13) were previously identified in a population of (NIH/Ola x M. spretus)F1 x NIH/Ola backcross animals. In this study the association of allele-specific mutations at the Skts intervals was examined in skin carcinoma samples. Several loci displayed allelic loss or duplication in skin carcinomas.

90 % of papillomas and carcinomas contain a mutation at codon 61 of the Hras1 gene (72 cM). In 23 out of 26 mouse tumors the Hras1 mutation occurred in the NIH/Ola-inherited allele. Hras1 maps near skin tumor susceptibility QTL Skts2 (64 cM on mouse Chromosome 7). A nearby marker, D7Mit12 (66 cM) also shows allelic imbalance involving the NIH/Ola allele.

On mouse Chromosome 6, preferential gain of the M. spretus allele or loss of the NIH/Ola allele was observed at D6Mit9 (36.5 cM) near Skts11 in 21 out of 21 carcinomas, and preferential gain of the M. spretus allele was observed at D6Mit15 (74 cM) near Skts12 in 14 out of 16 carcinomas.

On mouse Chromosome 9, preferential loss of the M. spretus allele or gain of the NIH/Ola allele was observed at D9Mit9 (48 cM) near Skts6 in 16 out of 23 carcinomas.

On mouse Chromosome 16, preferential loss of the M. spretus allele or gain of the NIH/Ola allele was observed at D16Mit2 (14.1 cM) near Skts9 in 10 out of 29 carcinomas.

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

J:59049

Susceptibility to skin papillomas in mice was analyzed in a backcross panel of 326 mice derived from (NIH/Ola female x M. spretus male)F1 female mice mated back to NIH/Ola male mice. Using negative binomial regression analysis, suggestive linkage of Skts11 with D6Mit97 (lod 3.17) was observed on mouse Chromosome 6. Skts11 confers susceptibility to either papilloma or carcinoma development in M. spretus. Another locus, Skts12 on mouse Chromosome 6 near D6Mit15 was also correlated with survival time, however the same phenotype may be encoded for by QTLs Skts11 and Skts12.

References

• Original: J:59049 Nagase H, et al., A subset of skin tumor modifier loci determines survival time of tumor-bearing mice. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15032-7
• All: 2 reference(s)