Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas.
Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas.
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DOI：
10.1371/journal.pone.0097201
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wakabayashi Y
中科院分区：
文献类型：
--
作者：
Okumura K;Saito M;Isogai E;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这些基因座，我们先前在大量[（FVB/N×MSM/Ms）×FVB/N] F1回交小鼠中鉴定出了对7号染色体上早期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，我们描述了一个相结合的同源定位和等位基因特异性改变分析的基因座7。我们使用连锁分析和同源小鼠品系，以完善的位置Stmm 1（皮肤肿瘤修饰MSM 1）基因座的遗传间隔约3 cM的近端染色体7。此外，我们使用F1回交和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 1基因座的区域，使其物理距离约为5.4 Mb。为了深入了解Stmm 1基因座的功能，我们对Stmm 1基因座的同源小鼠进行了长期BrdU标记实验。有趣的是，我们观察到在Stmm 1的MSM等位基因杂合或纯合的同源株中BrdU-LRC（标记保留细胞）减少。这些结果表明，Stmm 1的责任基因可能有影响乳头状瘤的发生在两个阶段的皮肤癌通过调节表皮静止干细胞。
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.
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DOI：
10.1186/1478-811x-8-23
发表时间：
2010-09-07
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Parri M;Chiarugi P
通讯作者：
Chiarugi P
影响因子：
4.6
作者：
Kangsamaksin, Thaned;Park, Heui Joon;Morris, Rebecca J.
通讯作者：
Morris, Rebecca J.
影响因子：
64.8
作者：
Ponder, BAJ
通讯作者：
Ponder, BAJ
影响因子：
2.9
作者：
Fujiwara, Kyoko;Igarashi, Jun;Nagase, Hiroki
通讯作者：
Nagase, Hiroki
影响因子：
30.8
作者：
NAGASE, H;BRYSON, S;BALMAIN, A
通讯作者：
BALMAIN, A