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首页> 外文期刊>Oncogene >Functional Fas (Cd95|[sol]|Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to |[gamma]|-radiation-induced thymic lymphoma
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Functional Fas (Cd95|[sol]|Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to |[gamma]|-radiation-induced thymic lymphoma

机译:自交系小鼠品系中的功能性Fas(Cd95 | [sol] | Apo-1)启动子多态性对|γ|辐射诱发的胸腺淋巴瘤表现出不同的易感性

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The Fas death receptor is a cell surface molecule involved in apoptosis as well as in proliferative or activating signals of many cells types, including T lymphocytes. Using quantitative real-time reverse transcription–PCR analysis, we confirm that expression of this gene is scarcely perceptible in thymic lymphomas induced by -irradiation in C57BL/6J mice. Notably, we also demonstrate for the first time that Fas expression is significantly upregulated in vivo both after single high dose of radiation and in thymic lymphoma-free mice. In addition, we determined its levels of expression in five mouse strains exhibiting different degrees of susceptibility (SPRET/Ei, SEG/Pas, BALB/cJ, C57BL/6J and RF/J). Interestingly, we found the highest levels of expression in SPRET/Ei and SEG/Pas strains (both derived from the Mus spretus species), which are known to have the most resistant phenotype, and the lowest levels in the most susceptible strains C57BL/6J and RF/J. DNA sequencing of the Fas promoter in all five strains showed many polymorphisms that can be classified into three functional haplotypes by using luciferase assays: (1) C57BL/6J and RF/J, (2) BALB/cJ and (3) SPRET/Ei and SEG/Pas. Promoter activities in response to single high doses of radiation correlated well with the levels of Fas expression and are consistent with the degree of strain susceptibility.
机译:Fas死亡受体是一种细胞表面分子,与细胞凋亡以及许多细胞类型(包括T淋巴细胞)的增殖或激活信号有关。使用定量实时逆转录-PCR分析,我们证实了该基因在C57BL / 6J小鼠的辐射诱发的胸腺淋巴瘤中几乎察觉不到。值得注意的是,我们还首次证明了单剂量高剂量放疗后和无胸腺淋巴瘤的小鼠体内Fas表达均显着上调。此外,我们确定了它在五种表现出不同程度敏感性的小鼠品系中的表达水平(SPRET / Ei,SEG / Pas,BALB / cJ,C57BL / 6J和RF / J)。有趣的是,我们发现SPRET / Ei和SEG / Pas菌株(均来自sspretus物种)中的表达水平最高,已知该菌株具有最强的耐药表型,而在最易感的菌株C57BL / 6J中表达水平最低。和RF / J。所有五个菌株中Fas启动子的DNA测序显示许多多态性,可通过荧光素酶测定将其分为三种功能性单倍型:(1)C57BL / 6J和RF / J,(2)BALB / cJ和(3)SPRET / Ei和SEG / Pas。响应单一高剂量辐射的启动子活性与Fas表达水平密切相关,并且与菌株易感性程度一致。

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