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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2014 > Volume 63 Number 3 > Megumi Saito, Kazuhiro Okumura, Ikuo Miura, Shigeharu Wakana, Ryo Kominami, Yuichi Wakabayashi

Identification of Stmm3 locus Conferring Resistance to Late-stage Chemically Induced Skin Papillomas on Mouse Chromosome 4 by Congenic Mappingand Allele-specific Alteration Analysis

Megumi Saito, Kazuhiro Okumura, Ikuo Miura, Shigeharu Wakana, Ryo Kominami, Yuichi Wakabayashi
1)Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan 2)Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, Riken Bioresource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan 3)Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8510, Japan
Abstract :

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 chemically induced skin papillomas on chromosome 4 and 7 with a large number of [(FVB/N × MSM/Ms) F1 × FVB/N] backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 4. We used linkage analysis and a congenic mouse strain, FVB.MSM-Stmm3 to refine the location of Stmm3 (Skin tumor modifier of MSM 3) locus within a physical interval of about 34 Mb on distal chromosome 4. In addition, we used patterns of allele-specific imbalances in tumors from N2 and N10 congenic mice to narrow down further the region of Stmm3 locus to a physical distance of about 25 Mb. Furthermore, immunohistochemical analysis showed papillomas from congenic mice had less proliferative activity. These results suggest that Stmm3 responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development.

Keywords :
allelic imbalance, congenic mice, DMBA-TPA, papilloma, tumor susceptibility

Date Deposited : 07 Apr 2015 10:31

Last Modified : 07 Apr 2015 10:31

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Volume 63, Number 3, - 2014

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