Altered body iron distribution and rmicrocytosis in mice deficient in iron regulatory protein 2 (IRP2)
Altered body iron distribution and rmicrocytosis in mice deficient in iron regulatory protein 2 (IRP2)
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DOI：
10.1182/blood-2005-04-1365
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发表时间：
2005-10-01
期刊：
影响因子：
20.3
通讯作者：
Hentze, MW
中科院分区：
文献类型：
--
作者：
Galy, B;Ferring, D;Hentze, MW
铁调节蛋白2（IRP 2）缺陷小鼠已被报道患有迟发性神经退行性疾病的未知机制。我们报告说，年轻的成年Irp 2（-/-）小鼠在哺乳动物体内的中央铁再循环途径，肝-骨髓-脾轴，与改变身体铁分布和受损的造血功能显示出铁管理不善的迹象。与野生型同窝小鼠相比，Irp 2（-/-）小鼠轻度小红细胞，血清血红蛋白水平和红细胞压积降低。血清铁和转铁蛋白饱和度不变，因此小红细胞症不是由于全身铁可用性明显下降。肝脏和十二指肠是铁负载的，而脾脏是铁缺乏的，与铁输出体ferroportin的表达减少有关。lrp 2（-/-）小鼠骨髓中转铁蛋白受体1（TfR 1）mRNA水平的降低可以合理地解释由于未能充分保护TfR 1 mRNA免受降解而导致的红细胞生成内在缺陷导致的小红细胞症。这项研究将一个经典的细胞调节因子。铁代谢与全身铁稳态和红细胞生成TfR 1表达的关系。此外，这项工作揭示了哺乳动物铁代谢的各个方面，这些方面可以或不能通过IRP 1的表达来补偿。
Iron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from late-onset neurodegeneration by an unknown mechanism. We report that young adult Irp2(-/-) mice display signs of iron mismanagement within the central iron recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with altered body iron distribution and compromised hematopoiesis. In comparison with wild-type littermates, Irp2(-/-) mice are mildly microcytic with reduced serum hemoglobin levels and hematocrit. Serum iron and transferrin saturation are unchanged, and hence microcytosis is not due to an overt decrease in systemic iron availability. The liver and duodenum are iron loaded, while the spleen is iron deficient, associated with a reduced expression of the iron exporter ferroportin. A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone marrow of lrp2(-/-) mice can plausibly explain the microcytosis by an intrinsic defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against degradation. This study links a classic regulator of cellular. iron metabolism to systemic iron homeostasis and erythropoietic TfR1 expression. Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1.