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Gene Review:

Skts1 - skin tumor susceptibility 1

Mus musculus

Peissel, B. et al., Balbín, M. et al., Mao, J.H. et al., Nagase, H. et al., Megosh, L.C. et al., et al.

Nagase, Mao, Balmain,

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Disease relevance of Skts1

We have investigated the effects of germ-line variants that influence skin tumor susceptibility loci on the patterns of somatic genetic alterations in mouse skin cancers [1].
The Car-derived Skts1 locus was linked with papilloma multiplicity and latency by a recessive inheritance of the susceptibility allele [2].

High impact information on Skts1

Loss of collagenase-2 confers increased skin tumor susceptibility to male mice [3].
We used the murine skin model of chemical carcinogenesis in genetic linkage analysis of three independent Mus musculus NIH/Ola x (Mus spretus x M. musculus NIH/Ola)F1 backcrosses, to identify a skin tumor susceptibility locus, Skts14, on proximal chromosome 7 [4].
A locus on chromosome 7 (Skts1) showed a highly significant interaction with Skts5 on chromosome 12 (P < 10(-16)), whereas additional significant interactions were detected between loci on chromosomes 4 and 5, and 16 and 15 [5].
Loss of tyrosinase activity confers increased skin tumor susceptibility in mice [6].
The enhancing effect of overexpression of an ornithine decarboxylase (Odc) transgene on skin tumor susceptibility can be modified by genetic loci present in several inbred mouse strains [7].

Biological context of Skts1

Analysis of these regions for genetic linkage with skin cancer phenotypes in 245 (Car-R x Car-S)F2 intercross mice, by using single nucleotide polymorphisms (SNPs), revealed significant linkage at a possible allelic form of the Skts1 locus, whose mapping region was shortened to a <5.5-cM interval near the Tyr locus [2].
Because we did not use a tumor-promotion protocol to induce tumors, most of the quantitative trait loci mapped in this study are distinct from skin tumor-susceptibility loci identified previously [8].

References

Allele-specific Hras mutations and genetic alterations at tumor susceptibility loci in skin carcinomas from interspecific hybrid mice. Nagase, H., Mao, J.H., Balmain, A. Cancer Res. (2003) [Pubmed]
Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci. Peissel, B., Zaffaroni, D., Pazzaglia, S., Manenti, G., Zanesi, N., Zedda, I., Rebessi, S., Covelli, V., Dragani, T.A., Saran, A. Mamm. Genome (2001) [Pubmed]
Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Balbín, M., Fueyo, A., Tester, A.M., Pendás, A.M., Pitiot, A.S., Astudillo, A., Overall, C.M., Shapiro, S.D., López-Otín, C. Nat. Genet. (2003) [Pubmed]
Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility. Mao, J.H., Saunier, E.F., de Koning, J.P., McKinnon, M.M., Higgins, M.N., Nicklas, K., Yang, H.T., Balmain, A., Akhurst, R.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
Epistatic interactions between skin tumor modifier loci in interspecific (spretus/musculus) backcross mice. Nagase, H., Mao, J.H., de Koning, J.P., Minami, T., Balmain, A. Cancer Res. (2001) [Pubmed]
Loss of tyrosinase activity confers increased skin tumor susceptibility in mice. Saran, A., Spinola, M., Pazzaglia, S., Peissel, B., Tiveron, C., Tatangelo, L., Mancuso, M., Covelli, V., Giovannelli, L., Pitozzi, V., Pignatiello, C., Milani, S., Dolara, P., Dragani, T.A. Oncogene (2004) [Pubmed]
Identification of an X-linked locus modifying mouse skin tumor susceptibility. George, K., Iacobucci, A., Uitto, J., O'Brien, T.G. Mol. Carcinog. (2005) [Pubmed]
Genetic control of polyamine-dependent susceptibility to skin tumorigenesis. Megosh, L.C., Hu, J., George, K., O'Brien, T.G. Genomics (2002) [Pubmed]

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