Coppola Giovanni, Choi Sang-Hyun, Santos Manuela M, Miranda Carlos J, Tentler Dmitri, Wexler Eric M, Pandolfo Massimo, Geschwind Daniel H
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine-UCLA, 710 Westwood Plaza, Los Angeles, CA 90095, USA.
Neurobiol Dis. 2006 May;22(2):302-11. doi: 10.1016/j.nbd.2005.11.014. Epub 2006 Jan 25.
Friedreich's ataxia (FRDA) is caused by reduction of frataxin levels to 5-35%. To better understand the biochemical sequelae of frataxin reduction, in absence of the confounding effects of neurodegeneration, we studied the gene expression profile of a mouse model expressing 25-36% of the normal frataxin levels, and not showing a detectable phenotype or neurodegenerative features. Despite having no overt phenotype, a clear microarray gene expression phenotype was observed. This phenotype followed the known regional susceptibility in this disease, most changes occurring in the spinal cord. Additionally, gene ontology analysis identified a clear mitochondrial component, consistent with previous findings. We were able to confirm a subset of changes in fibroblast cell lines from patients. The identification of a core set of genes changing early in the FRDA pathogenesis can be a useful tool in both clarifying the disease process and in evaluating new therapeutic strategies.
弗里德赖希共济失调（FRDA）是由铁调素水平降至5% - 35%所致。为了在不存在神经退行性变干扰效应的情况下，更好地理解铁调素减少的生化后果，我们研究了一种小鼠模型的基因表达谱，该模型表达的铁调素水平为正常水平的25% - 36%，且未表现出可检测到的表型或神经退行性特征。尽管没有明显的表型，但观察到了明显的微阵列基因表达表型。这种表型遵循了该疾病已知的区域易感性，大多数变化发生在脊髓中。此外，基因本体分析确定了明显的线粒体成分，这与先前的研究结果一致。我们能够证实患者成纤维细胞系中的一部分变化。确定在FRDA发病机制早期发生变化的一组核心基因，在阐明疾病过程和评估新的治疗策略方面都可能是一个有用的工具。
