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

Giovanni Coppola, Sang Hyun Choi, Manuela M. Santos, Carlos J. Miranda, Dmitri Tentler, Eric M. Wexler, Massimo Pandolfo, Daniel H. Geschwind

    Research output: Contribution to journalArticlepeer-review

    48 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)302-311
    Number of pages10
    JournalNeurobiology of Disease
    Volume22
    Issue number2
    DOIs
    Publication statusPublished - 2006 May

    Keywords

    • Frataxin
    • Friedreich's ataxia
    • Knockin/knockout
    • Microarray
    • Mouse model
    • Neurodegeneration

    ASJC Scopus subject areas

    • Neurology

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