The transcriptional regulator GON4L is required for viability and hematopoiesis in mice.
The transcriptional regulator GON4L is required for viability and hematopoiesis in mice.
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DOI：
10.1016/j.exphem.2021.04.001
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发表时间：
2021-06
影响因子：
2.6
通讯作者：
Colgan JD
中科院分区：
文献类型：
--
作者：
Colgan DF;Goodfellow RX;Colgan JD
Gon4l基因编码一个可能的转录调节因子，参与控制细胞的分化和增殖。在此之前，我们描述了一种名为Justy的突变小鼠品系，其中Gon4l产生的前-mRNA的剪接被破坏。这一缺陷严重减少了GON4L蛋白的表达，但不会取消GON4L蛋白的表达，并阻止了早期B系祖细胞的形成，表明GON4L是脊椎动物B细胞发育所必需的。然而，使斑马鱼Gon4l失效的突变损害了胚胎发生的几个方面，包括启动原始造血，认为该基因是多种脊椎动物发育途径所必需的。为了更好地了解Gon4l在哺乳动物中的重要性，我们创造了携带一种工程版本的Gon4l的小鼠，这种基因可以通过Cre介导的重组完全失活。携带灭活的Gon4l等位基因杂合子的小鼠未能产生任何纯合子缺失的后代，这表明Gon4l是哺乳动物的一个必需基因。与这一发现以及之前发表的结果一致，细胞培养研究表明，Gon4l的丢失阻止了细胞的增殖并影响了细胞的生存能力，这表明在控制细胞分裂和生存方面发挥了重要作用。使用混合骨髓嵌合体的研究证实，Gon4l是B细胞发育所必需的，但也表明它是维持所有造血细胞系的来源的明确的造血干/祖细胞所必需的。我们的发现揭示了Gon4l是哺乳动物的一个必需基因，它是形成整个造血系统所必需的。
The Gon4l gene encodes a putative transcriptional regulator implicated in the control of both cell differentiation and proliferation. Previously, we described a mutant mouse strain called Justy in which splicing of pre-mRNA generated from Gon4l is disrupted. This defect severely reduces, but does not abolish, GON4L protein expression, and blocks the formation of early B-lineage progenitors, suggesting Gon4l is required for B cell development in vertebrates. Yet, mutations that disable Gon4l in zebrafish impair several facets of embryogenesis that include the initiation of primitive hematopoiesis, arguing this gene is needed for multiple vertebrate developmental pathways. To better understand the importance of Gon4l in mammals, we created mice carrying an engineered version of Gon4l that can be completely inactivated by Cre-mediated recombination. Breeding mice heterozygous for the inactivated Gon4l allele failed to yield any homozygous-null offspring, demonstrating Gon4l is an essential gene in mammals. Consistent with this finding, as well previously published results, cell culture studies showed loss of Gon4l blocks cell proliferation and compromises viability, suggesting a fundamental role in the control of cell division and survival. Studies using mixed bone marrow chimeras confirmed Gon4l is required for B cell development, but also showed it is needed to maintain definitive hematopoietic stem/progenitor cells that are the source of all hematopoietic cell lineages. Our findings reveal Gon4l is an essential gene in mammals that is required to form the entire hematopoietic system.
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影响因子：
10.5
作者：
Yamaguchi, Teppei;Cubizolles, Fabien;Matthias, Patrick
通讯作者：
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DOI：
10.1073/pnas.1606297113
发表时间：
2016-07-05
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