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Series GSE15848 Query DataSets for GSE15848
Status Public on Jun 02, 2009
Title Functional genomic analysis of frataxin deficiency, Illumina data
Organism Mus musculus
Experiment type Expression profiling by array
Summary Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARγ pathway as a therapeutic target in Friedreich's ataxia

Friedreich's ataxia (FRDA), the most common inherited ataxia, is characterized by focal neurodegeneration, diabetes mellitus, and life-threatening cardiomyopathy. Frataxin, which is significantly reduced in patients with this recessive disorder, is a mitochondrial iron-binding protein, but how its deficiency leads to neurodegeneration and metabolic derangements is not known. We performed microarray analysis of heart and skeletal muscle in a mouse model of frataxin deficiency, and found molecular evidence of increased lipogenesis in skeletal muscle, and alteration of fiber-type composition in heart, consistent with insulin resistance and cardiomyopathy, respectively. Since the peroxisome proliferator-activated receptor gamma (PPARγ) pathway is known to regulate both processes, we hypothesized that dysregulation of this pathway could play a key role in frataxin deficiency. We confirmed this by showing a coordinate dysregulation of the PPARγ coactivator Pgc1a and transcription factor Srebp1 in cellular and animal models of frataxin deficiency, and in cells from FRDA patients, who have marked insulin resistance. Finally, we show that genetic modulation of the PPARγ pathway affects frataxin levels in vitro, supporting PPARγ as a novel therapeutic target in FRDA.
Overall design To compare frataxin deficient (KIKO) mice vs. WT, heart, skeletal muscle, and liver.
Contributor(s) Coppola G, Marmolino D, Lu D, Wang Q, Cnop M, Rai M, Acquaviva F, Cocozza S, Pandolfo M, Geschwind DH
Citation(s) 19376812
Submission date Apr 27, 2009
Last update date Jan 18, 2013
Contact name Giovanni Coppola
Phone 310-794-4172
Organization name UCLA
Department Psychiatry and Neurology
Lab Neurogenetics
Street address 1524 Gonda, 695 Charles Young Drive South
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL6100 Illumina mouseRef-8 v1.0 expression beadchip
Samples (22)
GSM398052 E3h
GSM398053 E6h
GSM398054 E7h
This SubSeries is part of SuperSeries:
GSE15849 Functional genomic analysis of frataxin deficiency
BioProject PRJNA123051

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE15848_RAW.tar 2.6 Mb (http)(custom) TAR
GSE15848_raw_data.txt.gz 2.3 Mb (ftp)(http) TXT
Processed data included within Sample table

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