Galy Bruno, Ferring-Appel Dunja, Kaden Sylvia, Gröne Hermann-Josef, Hentze Matthias W
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, Germany.
Cell Metab. 2008 Jan;7(1):79-85. doi: 10.1016/j.cmet.2007.10.006.
Iron regulatory proteins (IRPs) orchestrate the posttranscriptional regulation of critical iron metabolism proteins at the cellular level. Redundancy between IRP1 and IRP2 associated with embryonic lethality of doubly IRP-deficient mice has precluded the study of IRP function in vivo. Here we use Cre/Lox technology to generate viable organisms lacking IRP expression in a single tissue, the intestine. Mice lacking intestinal IRP expression develop intestinal malabsorption and dehydration postnatally and die within 4 weeks of birth. We demonstrate that IRPs control the expression of divalent metal transporter 1 (DMT1) mRNA and protein, a limiting intestinal iron importer. IRPs are also shown to be critically important to secure physiological levels of the basolateral iron exporter ferroportin. IRPs are thus essential for intestinal function and organismal survival and coordinate the synthesis of key iron metabolism proteins in the duodenum.
铁调节蛋白（IRPs）在细胞水平上协调关键铁代谢蛋白的转录后调控。IRP1和IRP2之间的冗余性与双IRP缺陷小鼠的胚胎致死性相关，这使得在体内研究IRP功能变得困难。在这里，我们使用Cre/Lox技术在单一组织——肠道中生成缺乏IRP表达的存活生物体。缺乏肠道IRP表达的小鼠在出生后会出现肠道吸收不良和脱水，并在出生后4周内死亡。我们证明，IRPs控制二价金属转运蛋白1（DMT1）mRNA和蛋白的表达，DMT1是一种限制肠道铁吸收的蛋白。研究还表明，IRPs对于确保基底侧铁输出蛋白铁转运蛋白的生理水平至关重要。因此，IRPs对于肠道功能和机体存活至关重要，并协调十二指肠中关键铁代谢蛋白的合成。
