Alteration of copper physiology in mice overexpressing the human Menkes protein ATP7A
Alteration of copper physiology in mice overexpressing the human Menkes protein ATP7A
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DOI：
10.1152/ajpregu.00806.2005
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发表时间：
2006-05-01
影响因子：
2.8
通讯作者：
Mercer, JFB
中科院分区：
文献类型：
--
作者：
Ke, BX;Llanos, RM;Mercer, JFB
门克斯蛋白（ATP7A）在铜缺乏症门克斯病中存在缺陷，是维持生理铜稳态的重要贡献者。为了更充分地研究ATP7A的作用，我们从鸡β -肌动蛋白复合启动子（CAG）中获得了表达人Menkes基因ATP7A的转基因小鼠。转基因小鼠在肺、心、肝、肾、小肠和脑中表达ATP7A，但没有表现出由人类蛋白表达引起的明显表型。免疫组化分析显示，ATP7A主要存在于心肌、肺平滑肌、肾远端小管、肠上皮细胞和肝细胞斑块，以及海马、小脑和脑脉络膜丛。在60天和300天大的小鼠中，大多数组织中的Cu浓度降低，与ATP7A在Cu外排中起作用一致。老年T22#2女性（24%）、T22#2男性（18%）和T25#5女性（23%）以及60日龄T22#2女性和男性（分别为23%和30%）的大脑中铜的减少最为明显。
The Menkes protein (ATP7A) is defective in the Cu deficiency disorder Menkes disease and is an important contributor to the maintenance of physiological Cu homeostasis. To investigate more fully the role of ATP7A, transgenic mice expressing the human Menkes gene ATP7A from chicken beta-actin composite promoter (CAG) were produced. The transgenic mice expressed ATP7A in lung, heart, liver, kidney, small intestine, and brain but displayed no overt phenotype resulting from expression of the human protein. Immunohistochemical analysis revealed that ATP7A was found primarily in the cardiac muscle, smooth muscle of the lung, distal tubules of the kidney, intestinal enterocytes, and patches of hepatocytes, as well as in the hippocampus, cerebellum, and choroid plexus of the brain. In 60-day- and 300-day-old mice, Cu concentrations were reduced in most tissues, consistent with ATP7A playing a role in Cu efflux. The reduction in Cu was most pronounced in the hearts of older T22#2 females (24%), T22#2 males (18%), and T25#5 females (23%), as well as in the brains of 60-day-old T22#2 females and males ( 23% and 30%, respectively).