Jiralerspong S, Liu Y, Montermini L, Stifani S, Pandolfo M
Centre de Recherche Louis-Charles Simard, Montréal, Québec, Canada.
Neurobiol Dis. 1997;4(2):103-13. doi: 10.1006/nbdi.1997.0139.
Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease caused either by an intronic GAA triplet repeat expansion that suppresses the expression of the frataxin gene on chromosome 9q13, or, rarely, by point mutations in the frataxin gene. We investigated the expression of the mouse frataxin homologue during embryonic development by Northern blot analysis and RNA in situ hybridization. Very faint expression could be detected from E10.5 in the neuroepithelium and more clearly from E12.5 in the developing central nervous system. At E14.5, frataxin was expressed at a much higher level that remained constant into the postnatal period. Maximum expression was observed in the spinal cord, particularly at the thoracolumbar level, and in the dorsal root ganglia. Significant levels of transcript could also be detected in the proliferating cells in the periventricular zone, in the cortical plates, in the heart, in the axial skeleton, and in some epithelial and mesenchymal tissues. Overall, the distribution of frataxin mRNA was in good accordance with previous data from Northern analysis of adult human tissues, the major discrepancy being the expression in mouse embryonic cerebral cortex which was not observed in adult human brain. The tissues expressing frataxin during development appear to be those that become dysfunctional or atrophied in FRDA. Overall, our data suggest that frataxin is a protein whose expression is cell-specific and developmentally regulated.
弗里德赖希共济失调（FRDA）是一种常染色体隐性退行性疾病，其病因要么是内含子GAA三联体重复扩增抑制了9号染色体q13上的铁调素基因的表达，要么是铁调素基因发生点突变（这种情况较为罕见）。我们通过Northern印迹分析和RNA原位杂交研究了小鼠铁调素同源物在胚胎发育过程中的表达情况。在胚胎第10.5天，可在神经上皮中检测到非常微弱的表达，而在发育中的中枢神经系统中，从胚胎第12.5天开始表达更明显。在胚胎第14.5天，铁调素的表达水平要高得多，并且在出生后一直保持恒定。在脊髓中观察到最高表达，特别是在胸腰段水平，以及在背根神经节中。在脑室周围区域的增殖细胞、皮质板、心脏、轴骨骼以及一些上皮和间充质组织中也能检测到显著水平的转录本。总体而言，铁调素mRNA的分布与先前对成人组织进行Northern分析的数据高度一致，主要差异在于在小鼠胚胎大脑皮质中的表达，而在成人大脑中未观察到这种表达。在发育过程中表达铁调素的组织似乎是那些在FRDA中会出现功能障碍或萎缩的组织。总体而言，我们的数据表明铁调素是一种其表达具有细胞特异性且受发育调控的蛋白质。
