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| Status |
Public on Jun 02, 2009 |
| Title |
Functional genomic analysis of frataxin deficiency, Agilent data |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| 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.
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| Overall design |
To compare frataxin deficient (KIKO) mice vs. WT, heart and skeletal muscle. Three replicates (KIKO vs WT), with dye swap
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| 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 |
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| Submission date |
Apr 27, 2009 |
| Last update date |
Dec 06, 2012 |
| Contact name |
Giovanni Coppola |
| E-mail(s) |
gcoppola@ucla.edu
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| Phone |
310-794-4172
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| Organization name |
UCLA
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| Department |
Psychiatry and Neurology
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| Lab |
Neurogenetics
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| Street address |
1524 Gonda, 695 Charles Young Drive South
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL891 |
Agilent-011978 Mouse Microarray G4121A (Feature Number version) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE15849 |
Functional genomic analysis of frataxin deficiency |
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| Relations |
| BioProject |
PRJNA123043 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE15843_RAW.tar |
66.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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