在唐氏综合征的小鼠模型中,三胞体抑制了Apc(Min) 介导的瘤
Thomas E Sussan1, Annan Yang, Fu Li
1Department of Physiology and The Institute for Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|January 4, 2008
概括
患有唐氏综合征 (三形 21) 的人可能患肠道瘤的发病率较低. 鼠标模型显示三症,特别是涉及Ets2基因,显著减少瘤发育,表明潜在的预防作用.
科学领域:
- 遗传学 是一个遗传学.
- 癌症生物学 癌症生物学
- 发展生物学 发展生物学
背景情况:
- 关于唐氏综合征 (三症组 21) 癌症发病率的流行病学研究产生了相互矛盾的结果.
- 了解积体症癌症风险的生物学基础至关重要.
研究的目的:
- 用小鼠模型研究三症和肠道瘤发病率之间的关系.
- 为了确定三症是否影响Apc(Min) 介导的肠道瘤发育.
主要方法:
- 利用了模仿唐氏综合征方面的一些状小鼠模型 (Ts65Dn,Ts1Rhr,Ms1Rhr).
- 在这些模型中,量化 Apc ((Min) 介导的肠道瘤数量.
- 分析了包括Ets2在内的特定基因在对瘤发育的剂量敏感影响中的作用.
主要成果:
- 在Ts65Dn和Ts1Rhr小鼠中,人类21号染色体的三胞体对象显著减少了肠道瘤的数量.
- 在Ms1Rhr小鼠中,对相同基因的单体化增加了瘤的数量.
- 确定了Ets2基因是对瘤发病率的剂量敏感影响的主要贡献者.
结论:
- 三胞胎瘤,特别是涉及到Ets2,对肠道瘤的发展具有保护作用.
- 过度表达Ets2作为抑制剂,与传统的瘤抑制有所区别.
- 提高Ets2和相关基因的调节可能会对癌症产生预防作用,不管是什么类型.
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