Identification of Stmm3 locus conferring resistance to late-stage chemically induced skin papillomas on mouse chromosome 4 by congenic mapping and allele-specific alteration analysis.
Identification of Stmm3 locus conferring resistance to late-stage chemically induced skin papillomas on mouse chromosome 4 by congenic mapping and allele-specific alteration analysis.
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DOI：
10.1538/expanim.63.339
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发表时间：
2014
影响因子：
2.4
通讯作者：
Wakabayashi Y
中科院分区：
文献类型：
--
作者：
Saito M;Okumura K;Miura I;Wakana S;Kominami R;Wakabayashi Y
全基因组关联研究表明，许多低转移率的癌症易感基因位点位于整个基因组中;然而，迄今为止，已经确定的基因数量非常有限。使用正向遗传学方法在小鼠皮肤癌模型中定位此类基因座，我们先前在大量[（FVB/N × MSM/Ms）F1 × FVB/N]回交小鼠中鉴定出对4号和7号染色体上化学诱导的皮肤乳头状瘤具有抗性的强遗传基因座。在这份报告中，我们描述了同源定位和等位基因特异性改变分析的4号染色体上的位点相结合。我们使用连锁分析和同源小鼠品系FVB. MSM-Stmm 3来细化Stmm 3（MSM 3的皮肤肿瘤修饰物）基因座在远端4号染色体上约34 Mb的物理间隔内的位置。此外，我们使用N2和N10同源小鼠肿瘤中等位基因特异性失衡的模式，进一步缩小Stmm 3基因座的区域，使其物理距离约为25 Mb。此外，免疫组化分析显示，同源小鼠的乳头状瘤具有较低的增殖活性。这些结果表明，Stmm 3的责任基因可能有影响乳头状瘤形成的两个阶段的皮肤癌通过调节乳头状瘤的生长，而不是发展。
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.
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影响因子：
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作者：
Kangsamaksin, Thaned;Park, Heui Joon;Morris, Rebecca J.
通讯作者：
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