Klomp L W, Gitlin J D
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis Children's Hospital, MO 63110, USA.
Hum Mol Genet. 1996 Dec;5(12):1989-96. doi: 10.1093/hmg/5.12.1989.
Aceruloplasminemia is an autosomal recessive disorder of iron metabolism characterized by progressive neurodegeneration of the retina and basal ganglia in association with inherited mutations of the ceruloplasmin gene. To begin to elucidate the pathogenesis of this disease, ceruloplasmin gene expression was examined in human brain and retinal tissue. RNA blot analysis and RNAse protection studies demonstrate ceruloplasmin-specific transcripts in multiple regions of the human brain, and biosynthetic studies reveal ceruloplasmin synthesis and secretion in these same regions. Consistent with these observations, in situ hybridization of central nervous system tissue utilizing ceruloplasmin cRNA probes reveals abundant ceruloplasmin gene expression in specific populations of glial cells associated with the brain microvasculature, surrounding dopaminergic melanized neurons in the substantia nigra and within the inner nuclear layer of the retina. Taken in the context of the clinical and pathological features observed in patients with aceruloplasminemia, these data reveal that glial cell-specific ceruloplasmin gene expression is essential for iron homeostasis and neuronal survival in the human central nervous system.
无铜蓝蛋白血症是一种常染色体隐性铁代谢紊乱疾病，其特征为视网膜和基底神经节进行性神经变性，并伴有铜蓝蛋白基因的遗传性突变。为了初步阐明该疾病的发病机制，研究人员检测了人脑和视网膜组织中铜蓝蛋白基因的表达。RNA印迹分析和RNA酶保护研究表明，在人脑的多个区域存在铜蓝蛋白特异性转录本，生物合成研究显示这些相同区域存在铜蓝蛋白的合成和分泌。与这些观察结果一致，利用铜蓝蛋白cRNA探针进行的中枢神经系统组织原位杂交显示，在与脑微血管相关的特定神经胶质细胞群体、黑质中围绕多巴胺能黑素化神经元以及视网膜内核层内，存在丰富的铜蓝蛋白基因表达。结合无铜蓝蛋白血症患者的临床和病理特征来看，这些数据表明，神经胶质细胞特异性铜蓝蛋白基因表达对于人类中枢神经系统中的铁稳态和神经元存活至关重要。
