Gene expression profiling in frataxin deficient mice: Microarray evidence for significant expression changes without detectable neurodegeneration

NEUROBIOLOGY OF DISEASE

卷:22

Article

Coppola, G ; Choi, SH ; Santos, MM ; Miranda, CJ ; Tentler, D ; Wexler, EM ; Pandolfo, M ; Geschwind, DH

关键词: Friedreich's ataxia;    microarray;    mouse model;    frataxin;    neurodegeneration;    knockin/knockout;   

DOI  :  10.1016/j.nbd.2005.11.014

来源: Elsevier

【 摘 要 】

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. (c) 2006 Elsevier Inc. All rights reserved.

【 授权许可】

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