Klomp L W, Farhangrazi Z S, Dugan L L, Gitlin J D
Edward Mallinckrodt Department off Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Clin Invest. 1996 Jul 1;98(1):207-15. doi: 10.1172/JCI118768.
Aceruloplasminemia is an autosomal recessive disorder resulting in neurodegeneration of the retina and basal ganglia in association with iron accumulation in these tissues. To begin to define the mechanisms of central nervous system iron accumulation and neuronal loss in this disease, cDNA clones encoding murine ceruloplasmin were isolated and characterized. RNA blot analysis using these clones detected a 3.7-kb ceruloplasmin-specific transcript in multiple murine tissues including the eye and several regions of the brain. In situ hybridization of systemic tissues revealed cell-specific ceruloplasmin gene expression in hepatocytes, the splenic reticuloendothelial system and the bronchiolar epithelium of the lung. In the central nervous system, abundant ceruloplasmin gene expression was detected in specific populations of astrocytes within the retina and the brain as well as the epithelium of the choroid plexus. Analysis of primary cell cultures confirmed that astrocytes expressed ceruloplasmin mRNA and biosynthetic studies revealed synthesis and secretion of ceruloplasmin by these cells. Taken together these results demonstrate abundant cell-specific ceruloplasmin expression within the central nervous system which may account for the unique clinical and pathologic findings observed in patients with aceruloplasminemia.
无铜蓝蛋白血症是一种常染色体隐性疾病，会导致视网膜和基底神经节神经变性，并伴有这些组织中铁的蓄积。为了初步确定该疾病中中枢神经系统铁蓄积和神经元丢失的机制，对编码小鼠铜蓝蛋白的cDNA克隆进行了分离和鉴定。使用这些克隆进行的RNA印迹分析在包括眼睛和脑的几个区域在内的多种小鼠组织中检测到了一个3.7kb的铜蓝蛋白特异性转录本。全身组织的原位杂交显示铜蓝蛋白基因在肝细胞、脾网状内皮系统和肺细支气管上皮细胞中呈细胞特异性表达。在中枢神经系统中，在视网膜和脑内特定的星形胶质细胞群以及脉络丛上皮中检测到丰富的铜蓝蛋白基因表达。原代细胞培养分析证实星形胶质细胞表达铜蓝蛋白mRNA，生物合成研究显示这些细胞合成并分泌铜蓝蛋白。这些结果共同表明中枢神经系统内存在丰富的细胞特异性铜蓝蛋白表达，这可能解释了无铜蓝蛋白血症患者中观察到的独特临床和病理表现。
