Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities
Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities
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DOI：
10.1002/j.1460-2075.1996.tb00949.x
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发表时间：
1996-10-15
期刊：
影响因子：
11.4
通讯作者：
Maki, RA
中科院分区：
文献类型：
--
作者：
McKercher, SR;Torbett, BE;Maki, RA
PU.1是转录因子ets家族的成员，并且仅在造血谱系的细胞中表达。PU.1 DNA结合结构域中的破坏的纯合子小鼠出生时存活，但在48小时内死于严重败血症。这些新生儿的分析显示缺乏成熟的巨噬细胞、中性粒细胞、B细胞和T细胞，尽管存在红细胞和巨核细胞。无效小鼠中淋巴定型和发育的缺乏不是绝对的，因为维持抗生素的小鼠在出生后3-5天开始发育正常外观的T细胞。相反，在这些老年小鼠中仍然检测不到成熟的B细胞。在骨髓谱系中，尽管在老年抗生素治疗的动物中缺乏巨噬细胞，但到第3天开始出现少数具有嗜中性粒细胞特征的细胞。虽然PU. 1蛋白似乎不是髓系和淋巴系定型所必需的，但它绝对是B细胞和巨噬细胞正常分化所必需的。
PU.1 is a member of the ets family of transcription factors and is expressed exclusively in cells of the hematopoietic lineage, Mice homozygous for a disruption in the PU.1 DNA binding domain are born alive but die of severe septicemia within 48 h, The analysis of these neonates revealed a lack of mature macrophages, neutrophils, B cells and T cells, although erythrocytes and megakaryocytes were present. The absence of lymphoid commitment and development in null mice was not absolute, since mice maintained on antibiotics began to develop normal appearing T cells 3-5 days after birth, In contrast, mature B cells remained undetectable in these older mice, Within the myeloid lineage, despite a lack of macrophages in the older antibiotic-treated animals, a few cells with the characteristics of neutrophils began to appear by day 3, While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages.