The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon.
The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon.
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发表时间：
2002-06
期刊：
影响因子：
4.6
通讯作者：
J. Katz;N. Perreault;Bree G. Goldstein;Catherine S. Lee;P. Labosky;V. Yang;K. Kaestner
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文献类型：
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作者：
J. Katz;N. Perreault;Bree G. Goldstein;Catherine S. Lee;P. Labosky;V. Yang;K. Kaestner
Klf 4（以前称为GKLF）是在皮肤、肺、胃肠道和几个其它器官的上皮中表达的锌指转录因子。体外研究表明Klf 4在细胞增殖和/或分化中起重要作用。Klf 4无效突变的纯合子小鼠在出生后15小时内死亡，并显示表皮中晚期分化结构的选择性扰动，但Klf 4在胃肠道中的功能尚未研究。为了解决这个问题，我们通过胚胎干细胞中的同源重组产生Klf 4（-/-）小鼠。在这项研究中，我们提供了第一个体内证据表明Klf 4是结肠杯状细胞特异性分化因子。Klf 4（-/-）小鼠在出生后第1天的结肠中表现出正常的细胞增殖和细胞死亡率。然而，Klf 4（-/-）小鼠显示结肠中杯状细胞数量减少90%，原位杂交显示杯状细胞特异性标记Muc 2表达异常，结肠上皮酸性粘蛋白的阿尔新蓝染色异常，超微结构分析显示缺乏正常的杯状细胞形态。所有其他上皮细胞类型均存在于Klf 4（-/-）小鼠的结肠中。总之，Klf 4在体内结肠上皮细胞分化中发挥着至关重要的作用。
Klf4 (formerly GKLF) is a zinc-finger transcription factor expressed in the epithelia of the skin, lungs, gastrointestinal tract and several other organs. In vitro studies have suggested that Klf4 plays an important role in cell proliferation and/or differentiation. Mice homozygous for a null mutation in Klf4 die within 15 hours of birth and show selective perturbation of late-stage differentiation structures in the epidermis, but the function of Klf4 in the gastrointestinal tract has not been investigated. To address this issue, we have generated Klf4(-/-) mice by homologous recombination in embryonic stem cells. In this study, we provide the first in vivo evidence that Klf4 is a goblet cell-specific differentiation factor in the colon. Klf4(-/-) mice exhibit normal cell proliferation and cell death rates in the colon on postnatal day 1. However, Klf4(-/-) mice demonstrate a 90% decrease in the number of goblet cells in the colon, show abnormal expression of the goblet cell-specific marker Muc2 by in situ hybridization, have abnormal staining of the colonic epithelium with Alcian Blue for acidic mucins, and lack normal goblet cell morphology by ultrastructural analysis. All other epithelial cell types are present in the colon of Klf4(-/-) mice. In summary, Klf4 plays a crucial role in colonic epithelial cell differentiation in vivo.