Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P
Department of Molecular Cell Biology, Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany.
Nature. 1999 Feb 25;397(6721):702-6. doi: 10.1038/17812.
Transcription factors with a basic helix-loop-helix (HLH) motif have been shown to be crucial for various cell differentiation processes during development of multicellular organisms. Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. Members of the Id family also promote cell proliferation, implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice. Id2-/- mice lack lymph nodes and Peyer's patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs, is barely detectable in the Id2-/- intestine. Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.
具有碱性螺旋-环-螺旋（HLH）基序的转录因子已被证明在多细胞生物发育过程中的各种细胞分化过程中至关重要。Id蛋白通过HLH结构域抑制这些转录因子的异二聚化伙伴，以显性负性方式抑制其功能。Id家族成员还促进细胞增殖，这意味着其在细胞分化控制中发挥作用。在此我们表明，Id2对小鼠的正常发育不可或缺。Id2基因敲除小鼠缺乏淋巴结和派尔集合淋巴结。然而，它们的脾脏结构正常，具有T细胞和B细胞区室以及明显的生发中心。在Id2基因敲除小鼠的肠道中，几乎检测不到产生淋巴毒素（次级淋巴器官发育的必需因子）的细胞群体。此外，纯合突变体显示自然杀伤（NK）细胞群体大幅减少，这是由于NK细胞前体存在内在缺陷所致。我们的结果表明，Id2在外周淋巴器官和NK细胞的生成中具有重要作用。
