Skts2^{M. spretus}
QTL Variant Detail

Summary

• QTL variant: Skts2^{M. spretus}
• Name: skin tumor susceptibility 2; M. spretus
• MGI ID: MGI:2156873
• QTL: Skts2 Location: Chr7:129922733-129922943 bp Genetic Position: Chr7, cM position of peak correlated region/allele: 73.19 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 resistance to skin tumorigenesis compared to NIH/Ola. (J:27733)
• Inheritance: Not Specified

Notes

Candidate Genes

J:65010

Segregation analysis of a (Car-R x Car-S)F2 intercross revealed association of coat color with skin tumor susceptibility. Phenotypically selected inbred lines Car-R and Car-S are derived from progenitor strains A/J, DBA/2J, P/J, CBA/J, SJL/J, BALB/cJ, SWR/J, and C57BR/6J. Animals resistant or susceptible to skin tumors after challenge with carcinogens were selected as progenitors for each successive generation in the Car-R and Car-S lines, respectively. By the eighth generation of inbreeding all Car-S mice had white coats and all Car-R mice had coats of various colors. Authors estimate 7-10 QTLs affect skin tumor susceptibility. A region on mouse chromosome 7 containing the albino locus, Tyr, and a skin tumor susceptibility QTL, Skts2, may be a candidatelocus.

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:27733

Susceptibility to skin papillomas in mice was analyzed in a backcross panel of 326 mice derived from (NIH female x M. spretus male)F1 female mice mated back to NIH male mice. Parental strain M. spretus is resistant to skin papilloma formation compared toparental strain NIH. 133 microsatellite markers were screened. Using MAPMAKER/QTL, significant linkage (Mann-Whitney U test) of Skts1 with D7Mit87 (27.8 cM, lod 6.99) and Skts2 with D7Mit43 (64 cM, lod 5.77) was observed on mouse Chromosome 7. The linkage of Skts2 with D7Mit43 was observed in female mice only. Multiple regression analysis supports the evidence for two loci on mouse Chromosome 7. Potential candidate genes mapping near Skts1 are Igf1r (33 cM) and Fah (42.6 cM). Potential candidate genes mapping near Skts2 are Fgfr2 (63 cM) and Hras1 (72.2 cM).

References

• Original: J:27733 Nagase H, et al., Distinct genetic loci control development of benign and malignant skin tumours in mice. Nat Genet. 1995 Aug;10(4):424-9
• All: 2 reference(s)