Veuthey Tania, Wessling-Resnick Marianne
Department of Genetics and Complex Diseases, Harvard School of Public Health Boston, MA, USA.
Front Pharmacol. 2014 Apr 22;5:82. doi: 10.3389/fphar.2014.00082. eCollection 2014.
The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat's pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat's pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis.
贝尔格莱德大鼠是二价金属转运体1(DMT1)缺乏的动物模型。该品系源自1966年首次报道的一项X射线照射实验。从那时起,贝尔格莱德大鼠的病理生理学有助于揭示铁平衡的重要性以及DMT1的作用。本综述讨论了我们目前对铁转运稳态的理解,并总结了DMT1功能的分子细节。我们描述了对贝尔格莱德大鼠的研究如何揭示DMT1在铁向红细胞的分布以及十二指肠铁吸收中的关键作用。贝尔格莱德大鼠的病理学扩展了我们对肝脏铁处理、肺和嗅觉铁转运以及脑铁摄取和肾脏铁处理的认识。例如,由于铁和锰都是由DMT1转运的必需金属,因此已经发现了它们之间的代谢关系。贝尔格莱德大鼠的病理生理特征为我们提供了一个独特而有趣的动物模型来理解铁稳态。