Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation.
Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation.
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DOI：
10.1182/blood-2005-09-3596
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发表时间：
2006-06-15
期刊：
影响因子：
20.3
通讯作者：
Sexl V
中科院分区：
文献类型：
--
作者：
Hoelbl A;Kovacic B;Kerenyi MA;Simma O;Warsch W;Cui Y;Beug H;Hennighausen L;Moriggl R;Sexl V
Stat5转录因子Stat5a和Stat5b参与了淋巴系的发育和转化。大多数研究使用了Stat5a/b缺陷小鼠，其中基因靶向扰乱了第一个蛋白质编码外显子，导致N端截短形式的Stat5a/b(Stat5a/bΔN/ΔN小鼠)的表达。我们现在重新分析了Stat5a/b空/空小鼠的淋巴发育，这些小鼠的Stat5a/b基因位点完全缺失。少数存活的Stat5a/bnul/空小鼠缺乏CD8+T淋巴细胞。在Stat5a/BFL/fl lck-cre转基因动物中也发现CD8+T细胞的大量减少。γδT细胞受体阳性(γδTcr+)细胞在Stat5a/bΔN/ΔN小鼠中正常表达，而在Stat5a/bNull/Null动物中完全缺失。此外，在Stat5a/bNull/Null小鼠中，B细胞成熟在前B细胞阶段被取消，而Stat5a/bΔN/ΔN B淋巴样细胞发育到B细胞前阶段。用胎肝细胞培养进行的体外分析证实了这一观察结果。最引人注目的是，Stat5a/bNull/Null细胞对Abelson癌基因诱导的转化和白血病的发生具有抵抗力，而Stat5a/bΔN/ΔN来源的细胞更容易转化。这些发现显示了Stat5a/b、ΔN/ΔN和Stat5a/bNull/空小鼠明显的淋巴缺陷，并确定了Stat5a/b的N末端在B淋巴样转化中的新功能。
The Stat5 transcription factors Stat5a and Stat5b have been implicated in lymphoid development and transformation. Most studies have employed Stat5a/b-deficient mice where gene targeting disrupted the first protein-coding exon, resulting in the expression of N-terminally truncated forms of Stat5a/b (Stat5a/bΔN/ΔN mice). We have now reanalyzed lymphoid development in Stat5a/bnull/null mice having a complete deletion of the Stat5a/b gene locus. The few surviving Stat5a/bnull/null mice lacked CD8+ T lymphocytes. A massive reduction of CD8+ T cells was also found in Stat5a/bfl/fl lck-cre transgenic animals. While γδ T-cell receptor–positive (γδTCR+) cells were expressed at normal levels in Stat5a/bΔN/ΔN mice, they were completely absent in Stat5a/bnull/null animals. Moreover, B-cell maturation was abrogated at the pre–pro-B-cell stage in Stat5a/bnull/null mice, whereas Stat5a/bΔN/ΔN B-lymphoid cells developed to the early pro-B-cell stage. In vitro assays using fetal liver-cell cultures confirmed this observation. Most strikingly, Stat5a/bnull/null cells were resistant to transformation and leukemia development induced by Abelson oncogenes, whereas Stat5a/bΔN/ΔN-derived cells readily transformed. These findings show distinct lymphoid defects for Stat5a/bΔN/ΔN and Stat5a/bnull/null mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation.
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DOI：
10.1006/mcbr.2000.0231
发表时间：
2000-05-01
期刊：
Molecular Cell Biology Research Communications
影响因子：
--
作者：
de Groot, Rolf P.;Raaijmakers, Jan A. M.;Koenderman, Leo
通讯作者：
Koenderman, Leo
影响因子：
4.4
作者：
Burchill, MA;Goetz, CA;Farrar, MA
通讯作者：
Farrar, MA
影响因子：
4.4
作者：
Goetz, CA;Harmon, IR;Farrar, MA
通讯作者：
Farrar, MA
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
4.4
作者：
Kelly, J;Spolski, R;Leonard, WJ
通讯作者：
Leonard, WJ