Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation
Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation
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DOI：
10.1128/mcb.00865-13
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发表时间：
2014-03-01
影响因子：
5.3
通讯作者：
Furukawa, Tatsuhiko
中科院分区：
文献类型：
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作者：
Yamamoto, Masatatsu;Arimura, Hiroshi;Furukawa, Tatsuhiko
Abcb10是ABC转运蛋白家族的10个成员，是线粒体内膜上与丝裂铁蛋白-1(Slc25a37)和铁络合酶(Fech)的复合体的一部分，负责子宫内血红素的生物合成。然而，目前尚不清楚Abcb10基因的缺失是否会导致成年小鼠的病理变化。在这里，我们表明Abcb10(-/-)小鼠缺乏血红素生物合成和红细胞生成能力，并在怀孕中期死亡。此外，我们还获得了Abcb10(F/-)；Mx1-Cre小鼠，其中删除了Abcb10在造血细胞中的表达，显示了原卟啉IX在网织红细胞中的蓄积和成熟停滞。Abcb10(-/-)造血细胞的电子显微镜图像显示线粒体铁沉积显著增加。这些结果提示了Abcb10在血红素生物合成中的关键作用，并为红细胞生成性原红细胞增多症和铁粒母细胞贫血的发病机制提供了新的见解。
Abcb10, member 10 of the ABC transporter family, is reportedly a part of a complex in the mitochondrial inner membrane with mitoferrin-1 (Slc25a37) and ferrochelatase (Fech) and is responsible for heme biosynthesis in utero. However, it is unclear whether loss of Abcb10 causes pathological changes in adult mice. Here, we show that Abcb10(-/-) mice lack heme biosynthesis and erythropoiesis abilities and die in midgestation. Moreover, we generated Abcb10(F/-); Mx1-Cre mice, with Abcb10 in hematopoietic cells deleted, which showed accumulation of protoporphyrin IX and maturation arrest in reticulocytes. Electron microscopy images of Abcb10(-/-) hematopoietic cells showed a marked increase of iron deposits at the mitochondria. These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia.