Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor
Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor
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DOI：
10.1016/s1074-7613(03)00168-7
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发表时间：
2003-07-01
期刊：
影响因子：
32.4
通讯作者：
Goodnow, CC
中科院分区：
文献类型：
--
作者：
Papathanasiou, P;Perkins, AC;Goodnow, CC
理解血淋巴系统的一个中心问题是在小鼠中产生适当的突变等位基因，以揭示调控基因的功能。在这里，我们描述了一种小鼠品系，塑料，在Ikaros的锌指中具有点突变，该点突变破坏DNA结合，但保留了全长蛋白质到更高阶复合物中的有效组装。Ikaros（Plastic）纯合子是胚胎致死的，具有在终末红细胞和粒细胞分化中的严重缺陷、过度的巨噬细胞形成和淋巴细胞生成受阻，而杂合子在淋巴细胞分化中显示部分阻断。与消融全长蛋白质的Ikaros等位基因的更受限制的效应的对比突出了在哺乳动物中产生隐性生态位填充等位基因的重要性，所述隐性生态位填充等位基因在多分子组装中不产生空隙的情况下发挥功能。
A central issue in understanding the hematolymphoid system is the generation of appropriate mutant alleles in mice to reveal the function of regulatory genes. Here we describe a mouse strain, Plastic, with a point mutation in a zinc finger of Ikaros that disrupts DNA binding but preserves efficient assembly of the full-length protein into higher order complexes. Ikaros(Plastic) homozygosity is embryonically lethal with severe defects in terminal erythrocyte and granulocyte differentiation, excessive macrophage formation, and blocked lymphopoiesis, while heterozygotes display a partial block in lymphocyte differentiation. The contrast with more circumscribed effects of Ikaros alleles that ablate the full-length protein highlights the importance in mammals of generating recessive niche-filling alleles that inactivate function without creating a void in multi-molecular assemblies.