New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK
New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK
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DOI：
10.1186/1471-2156-8-39
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发表时间：
2007-06-28
期刊：
影响因子：
2.9
通讯作者：
Nagase, Hiroki
中科院分区：
文献类型：
--
作者：
Fujiwara, Kyoko;Igarashi, Jun;Nagase, Hiroki
背景：小鼠品系之间的多种皮肤癌易感性使得确定负责皮肤癌发展的基因成为可能。到目前为止，通过使用两阶段皮肤癌模型[由7.12-二甲基苯(a)蒽(DMBA)/12- o-十四烷酰基苯酚-13-乙酸（TPA）诱导]，已经绘制了15个皮肤肿瘤易感性的Skts位点。一些相关基因已经在野生来源的优势抗性繁殖鼠小鼠中被鉴定出来，其中一个已被证实是多种人类癌症的低外显率癌症易感基因。结果：在本研究中，我们发现野生来源的PWK小鼠通过两阶段皮肤癌变方案治疗后没有出现肿瘤。当与高度敏感的菌株FVB杂交时，该表型具有显性抗性。通过分析PWK和FVB之间的F1回交代，我们发现在4号染色体上的新位点Skts-fp1和1、3、11、12和14号染色体上的显著连锁与皮肤肿瘤易感性有关。Skts-fp1包含Skts7区间，该区间先前由Mus spretus和NIH回交绘制。我们还在雌性种群中观察到1号和2号染色体上的暗示性连锁，而在雄性种群中仅观察到14号和15号染色体上的暗示性连锁。D11Mit339和D16Mit14标记间存在显著的遗传互作。结论：对这一新杂交的分析可能有助于确定小鼠皮肤癌易感性的基因，并可能揭示它们之间的生物学相互作用。
Background: A variety of skin cancer susceptibility among mouse strains has allowed identification of genes responsible for skin cancer development. Fifteen Skts loci for skin tumour susceptibility have been mapped so far by using the two-stage skin carcinogenesis model [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)]. A few responsible genes have been identified using wild-derived dominant resistant Mus spretus mice, and one has been confirmed as a low penetrance cancer susceptibility gene in a variety of human cancers.Results: In the present study, we found that wild-derived PWK mice developed no tumour by treatment with the two-stage skin carcinogenesis protocol. This phenotype is dominant resistant when crossed with the highly susceptible strain FVB. By analyzing the F1 backcross generation between PWK and FVB, we found empirical evidence of significant linkage at the new loci Skts-fp1 on chromosome 4 and suggestive linkage on chromosomes 1, 3, 11, 12 and 14 for skin tumour susceptibility. Skts-fp1 includes the Skts7 interval, which was previously mapped by a Mus spretus and NIH backcross. We also observed suggestive linkage on chromosomes 1 and 2 in the female population only, while suggestive linkage on chromosomes 14 and 15 only was observed in the male population. A significant genetic interaction was seen between markers of D11Mit339 and D16Mit14.Conclusion: Analysis of this new cross may facilitate the identification of genes responsible for mouse skin cancer susceptibility and may reveal their biological interactions.