Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas.
Genome-wide association studies have revealed that many low-penetrance cancer susceptibility loci are located throughout the genome; however, a very limited number of genes have been identified so far. Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to early-stage chemically induced skin papillomas on chromosome 7 with a large number of [(FVB/N×MSM/Ms)×FVB/N] F1 backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 7. We used linkage analysis and congenic mouse strains to refine the location of Stmm1 (Skin tumor modifier of MSM 1) locus within a genetic interval of about 3 cM on proximal chromosome 7. In addition, we used patterns of allele-specific imbalances in tumors from F1 backcross and N10 congenic mice to narrow down further the region of Stmm1 locus to a physical distance of about 5.4 Mb. To gain the insight into the function of Stmm1 locus, we carried out a long term BrdU labelling experiments with congenic mice containing Stmm1 locus. Interestingly, we observed a decrease of BrdU-LRCs (Label Retaining Cells) in a congenic strain heterozygous or homozygous for MSM allele of Stmm1. These results suggest that Stmm1 responsible genes may have an influence on papillomagenesis in the two-stage skin carcinogenesis by regulating epidermal quiescent stem cells.
Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
Kazuhiro
K
Okumura
Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
Megumi
M
Saito
Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
Eriko
E
Isogai
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, Riken Bioresource Center, Tsukuba, Ibaraki, Japan.
Ikuo
I
Miura
Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, Riken Bioresource Center, Tsukuba, Ibaraki, Japan.
Shigeharu
S
Wakana
Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
Ryo
R
Kominami
Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
Yuichi
Y
Wakabayashi
D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D008040:Genetic Linkage; D056426:Genetic Loci; D051379:Mice; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology