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

51 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
Externally publishedYes

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

Fingerprint

Dive into the research topics of 'Gene expression profiling in frataxin deficient mice: Microarray evidence for significant expression changes without detectable neurodegeneration'. Together they form a unique fingerprint.

Cite this