Poss K D, Tonegawa S
Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10919-24. doi: 10.1073/pnas.94.20.10919.
The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.
对于诸如红细胞生成等必需的哺乳动物生物学活动而言，大部分铁被认为是从细胞血红素蛋白中重新利用的。在此，我们培育出了缺乏功能性血红素加氧酶1（Hmox1；EC 1.14.99.3）的小鼠，该酶可将血红素分解为胆绿素、一氧化碳和游离铁，以评估其在铁稳态中的作用。缺乏Hmox1的成年小鼠出现了与血清铁水平异常降低相关的贫血，但肝脏和肾脏中铁蓄积，导致大分子氧化损伤、组织损伤和慢性炎症。我们的结果表明，Hmox1通过促进铁从肝脏和肾脏细胞中释放而具有重要的再循环作用，并描述了一种人类铁代谢紊乱的小鼠模型。
