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| Status |
Public on Mar 13, 2013 |
| Title |
Expression data for 2-month-old wild type and Tfam-SCKO (MPZ-Tfam KO) sciatic nerves |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Gene expression analysis of 2-month-old Ctrl and Tfam-SCKO mice. At this age mitochondrial function is disrupted in the Schwann cells of Tfam-SCKO mice ,but their nerves display only very limited pathology.
Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells, SCs) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response through actions of heme-regulated inhibitor kinase (HRI), and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines, an intermediate of fatty acid b-oxidation. Importantly, we show that acylcarnitines are released from SCs and induce axonal degeneration. A maladaptive integrated stress response as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies.
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| Overall design |
Total RNA samples were prepared by isolating and pooling RNA from three different 2-month-old MPZ-Tfam KO and Ctrl mice. 2 replicates per genotype were used in this experiment and they were prepared entirely independently.
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| Contributor(s) |
Viader A, Milbrandt J |
| Citation missing |
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| Submission date |
Feb 23, 2013 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Nobish Varghese |
| E-mail(s) |
nvarghese@path.wustl.edu
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| Organization name |
Washington University in St.Louis
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| Street address |
4444 Forest Park Ave.
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| City |
StLouis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA192904 |
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