title: 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.
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine-UCLA, 710 Westwood Plaza, Los Angeles, CA 90095, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Choi
authors.forename: Manuela M
authors.initials: MM
authors.lastname: Santos
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Miranda
authors.forename: Dmitri
authors.initials: D
authors.lastname: Tentler
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wexler
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
mesh_terms: D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin