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

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Author(s)

    • SAITO Megumi Saito Megumi
    • Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • OKUMURA Kazuhiro Okumura Kazuhiro
    • Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • MIURA Ikuo [他] Miura Ikuo
    • Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, Riken Bioresource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
    • Wakana Shigeharu
    • Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, Riken Bioresource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
    • Kominami Ryo
    • Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8510, Japan
    • Wakabayashi Yuichi
    • Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, 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) F<sub>1</sub> × 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-<i>Stmm3</i> to refine the location of <i>Stmm3</i> (<u>S</u>kin <u>t</u>umor <u>m</u>odifier of <u>M</u>SM <u>3</u>) 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 N<sub>2</sub> and N<sub>10</sub> congenic mice to narrow down further the region of <i>Stmm3</i> 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 <i>Stmm3</i> responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development.

Journal

  • Experimental Animals

    Experimental Animals 63(3), 339-348, 2014

    Japanese Association for Laboratory Animal Science

Codes

  • NII Article ID (NAID)
    130004677828
  • NII NACSIS-CAT ID (NCID)
    AA11032321
  • Text Lang
    ENG
  • ISSN
    1341-1357
  • NDL Article ID
    025599270
  • NDL Call No.
    Z54-H752
  • Data Source
    NDL  J-STAGE 
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