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

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.

Keywords

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