Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2013 Jul 31;8(7):e70022. doi: 10.1371/journal.pone.0070022. Print 2013.
Hematopoiesis is regulated by transcription factors that induce cell fate and differentiation in hematopoietic stem cells into fully differentiated hematopoietic cell types. The transcription factor zinc finger protein 148 (Zfp148) interacts with the hematopoietic transcription factor Gata1 and has been implicated to play an important role in primitive and definitive hematopoiesis in zebra fish and mouse chimeras. We have recently created a gene-trap knockout mouse model deficient for Zfp148, opening up for analyses of hematopoiesis in a conventional loss-of-function model in vivo. Here, we show that Zfp148-deficient neonatal and adult mice have normal or slightly increased levels of hemoglobin, hematocrit, platelets and white blood cells, compared to wild type controls. Hematopoietic lineages in bone marrow, thymus and spleen from Zfp148 (gt/gt) mice were further investigated by flow cytometry. There were no differences in T-cells (CD4 and CD8 single positive cells, CD4 and CD8 double negative/positive cells) in either organ. However, the fraction of CD69- and B220-positive cells among lymphocytes in spleen was slightly lower at postnatal day 14 in Zfp148 (gt/gt) mice compared to wild type mice. Our results demonstrate that Zfp148-deficient mice generate normal mature hematopoietic populations thus challenging earlier studies indicating that Zfp148 plays a critical role during hematopoietic development.
造血是由转录因子调节的，这些转录因子诱导造血干细胞的细胞命运和分化为完全分化的造血细胞类型。转录因子锌指蛋白 148（Zfp148）与造血转录因子 Gata1 相互作用，已被证明在斑马鱼和小鼠嵌合体的原始和定型造血中发挥重要作用。我们最近创建了一个基因捕获敲除小鼠模型，该模型缺乏 Zfp148，为体内常规功能丧失模型中的造血分析开辟了道路。在这里，我们表明，与野生型对照相比，Zfp148 缺陷型新生和成年小鼠的血红蛋白、血细胞比容、血小板和白细胞水平正常或略有增加。通过流式细胞术进一步研究了 Zfp148（gt/gt）小鼠骨髓、胸腺和脾脏中的造血谱系。在任何器官中，T 细胞（CD4 和 CD8 单阳性细胞、CD4 和 CD8 双阴性/阳性细胞）均无差异。然而，与野生型小鼠相比，Zfp148（gt/gt）小鼠脾脏中 CD69-和 B220-阳性细胞在出生后第 14 天的淋巴细胞中的比例略低。我们的结果表明，Zfp148 缺陷型小鼠产生正常成熟的造血群体，这挑战了早期表明 Zfp148 在造血发育中发挥关键作用的研究。
