Leone A, Hamer D H
Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20205.
Experientia Suppl. 1987;52:477-80. doi: 10.1007/978-3-0348-6784-9_48.
Menkes' kinky hair disease, a lethal X-linked recessive trait, is characterized by abnormal copper accumulation in several non-hepatic tissues. The level of many copper enzymes is severely reduced, leading to damage of the connective and nervous tissues of the patients. Cultured skin fibroblasts from Menkes' patients retain more copper then normal controls, and the excess metal is bound to metallothionein. Low doses of copper in the media induce MT gene transcription in Menkes' but not in normal cells. Transfection experiments using a plasmid containing the mouse MT-I promoter fused to the enzyme chloramphenicol acetyl transferase show that the activation of the mMTI promoter is in trans. Two other effects are observed in Menkes' cells: (a) two heat-shock like proteins are synthesized in response to low doses of copper in the growth medium, and (b) Menkes' cells are more sensitive then normal fibroblasts to copper toxicity. Our interpretation of these results supports a model for a defect in one or more steps in copper metabolism or transport.
门克斯卷发综合征是一种致命的X连锁隐性性状疾病，其特征是在多个非肝脏组织中铜蓄积异常。许多铜酶的水平严重降低，导致患者的结缔组织和神经组织受损。门克斯病患者的培养皮肤成纤维细胞比正常对照保留更多的铜，并且过量的金属与金属硫蛋白结合。培养基中低剂量的铜可诱导门克斯病细胞而非正常细胞中的MT基因转录。使用含有与氯霉素乙酰转移酶融合的小鼠MT-I启动子的质粒进行的转染实验表明，mMTI启动子的激活是反式的。在门克斯病细胞中还观察到另外两种效应：（a）生长培养基中低剂量的铜会诱导合成两种热休克样蛋白，以及（b）门克斯病细胞比正常成纤维细胞对铜毒性更敏感。我们对这些结果的解释支持了铜代谢或转运中一个或多个步骤存在缺陷的模型。
