Genetic defects in copper metabolism
Genetic defects in copper metabolism
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DOI：
10.1093/jn/133.5.1527s
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发表时间：
2003-05-01
影响因子：
4.2
通讯作者：
Harris, ZL
中科院分区：
文献类型：
--
作者：
Shim, H;Harris, ZL
铜代谢的遗传缺陷突显了哺乳动物系统为维持正常铜平衡而发展起来的微妙平衡。门克斯病、斑驳小鼠、Atox-1缺陷小鼠和CTR1基因敲除小鼠揭示了充足的铜摄入量在胚胎发育和早期发育中的重要性，特别是在中枢神经系统。与过量铜相关的毒性表现在威尔逊病、中毒乳鼠、LEC大鼠和贝德灵顿梗犬的铜中毒，表明细胞对铜超载的深刻敏感性，特别是在大脑和肝脏。铜蓝蛋白(CP)含有人体血清中95%的铜，这种蛋白的遗传缺失会导致糖尿病、视网膜退化和神经退化。尽管铜代谢正常，但铜型纤溶酶原激活症患者和CP基因敲除小鼠已经扰乱了铁平衡和轻微的肝脏铜滞留。这些铜代谢的遗传性紊乱为铜的稳态调节机制提供了有价值的见解，并为进一步剖析这种必需金属在健康和疾病中的作用提供了模型。
Genetic defects in copper metabolism highlight the delicate balance mammalian systems have developed to maintain normal copper homeostasis. Menkes disease, the mottled mouse, the Atox-1-deficient mouse and the ctr1 knockout mouse reveal the importance of adequate copper intake during embryogenesis and early development, especially in the central nervous system. The toxicity associated with excess copper as manifest in Wilson disease, the toxic milk mouse, the LEC rat and copper toxicosis in the Bedlington terrier demonstrate the profound cellular susceptibility to copper overload, in particular, in the brain and liver. Ceruloplasmin (Cp) contains 95% of the copper found in human serum, and inherited loss of this protein results in diabetes, retinal degeneration and neurodegeneration. Despite normal copper metabolism, aceruloplasminemic patients and the Cp knockout mouse have disturbed iron homeostasis and mild hepatic copper retention. These genetic disorders of copper metabolism provide valuable insight into the mechanisms regulating copper homeostasis and models to further dissect the role of this essential metal in health and disease.