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 language | English |
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Pages (from-to) | 302-311 |
Number of pages | 10 |
Journal | Neurobiology of Disease |
Volume | 22 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2006 May |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by a research grant from Friedreich's Ataxia Research Alliance/MDA Seek-A-Miracle to GC and DHG, the William Smith Memorial fund gift to DHG, and by the National Institutes of Health (grant no. NS34192) to MP.
Keywords
- Frataxin
- Friedreich's ataxia
- Knockin/knockout
- Microarray
- Mouse model
- Neurodegeneration
ASJC Scopus subject areas
- Neurology