Suppression of Pu.1 function results in expanded myelopoiesis in zebrafish

Suppression of Pu.1 function results in expanded myelopoiesis in zebrafish
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Pu.1 功能的抑制导致斑马鱼骨髓细胞生成扩大

DOI:
10.1038/leu.2013.67
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发表时间:
2013-03
期刊:
影响因子:
11.4
通讯作者:
Liao, W.
Liao, W.
中科院分区:
医学1区
文献类型:
--
作者:
Leung, A. Y. H.;Zhang, W.;Wen, Z.;Liao, W.

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聚氨酯。1是ets家族转录因子的一员,它对于早期髓系祖细胞的产生以及骨髓形成过程中单核细胞与粒细胞谱系的确定是必不可少的。除了早期在骨髓形成中的功能外,PU。据报道,1也参与小鼠和人类的白血病发生。研究表明,PU。1在人急性髓性白血病(AML)患者、5、6和PU中表达下调。在一项涉及126例AML患者的研究中,约7%的患者发现1个突变。7同样,减少PU。1活性导致小鼠AML。由于其独特的优势,斑马鱼已被用作研究发育生物学和人类疾病许多方面的有前途的模型。10通过靶向诱导局部病变的基因组(TILLING)方法,我们获得了一个拟态的pu。1斑马鱼等位基因1G242D),它在Pu. 1蛋白的DNA结合区域中含有一个点突变。这种突变不影响pu。但破坏了Pu. 1蛋白的稳定,导致Pu. 1活性降低。3
PU. 1 is a member of Ets-family transcription factors, which is indispensable for generating early myeloid progenitors1 and for the determination of monocytic versus granulocytic lineages during myelopoiesis. 2, 3 Apart from its early function in myelopoiesis, PU. 1 is also reported to be involved in leukemogenesis in mice and human. 4 It has been shown that PU. 1 expression is downregulated in human acute myeloid leukemia (AML) patients, 5, 6 and PU. 1 mutations are found in about 7% of the patients in a study involving 126 AML patients. 7 Likewise, reduction of PU. 1 activity leads to AML in mice. 8, 9Owing to its unique advantages, zebrafish has been utilized as a promising model for studying many aspects of developmental biology and human diseases. 10 Through targeting induced local lesions in genomes (TILLING) approach, we obtained a hypomorphic pu. 1 zebrafish allele (pu. 1G242D), which harbors a point mutation in the DNA binding domain of the Pu. 1 protein. 3 This mutation does not affect pu. 1 transcription but destabilize Pu. 1 protein, resulting in a reduction of Pu. 1 activity. 3
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发表时间: 2005-05-02
期刊: The Journal of experimental medicine
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