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Published on: December 12, 2016
Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental Autoimmune Myasthenia Gravis in Rats
Henry J Kaminski1, Keiichi Himuro2, Jumana Alshaikh1
1Department of Neurology, George Washington University Washington, DC, USA.
Abstract:
The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM. Profiling results were validated by qPCR. Across the three muscles between the experiment and control groups, 359 probes (1.16%) with greater than 2-fold changes in expression in 7 of 9 series pairwise comparisons from 31,090 probes were identified with approximately two-thirds being increased. The three muscles shared 16 genes with increased expression and 6 reduced expression. Functional annotation demonstrated that these common expression changes fell predominantly into categories of metabolism, stress response, and signaling. Evaluation of specific gene function indicated that EAMG led to a change to oxidative metabolism. Genes related to muscle regeneration and suppression of immune response were activated. Evidence of a differential immune response among muscles was not evident. Each muscle had a distinct RNA profile but with commonality in gene categories expressed that are focused on muscle repair, moderation of inflammation, and oxidative metabolism.
Insights
Myasthenia gravis (MG) affects skeletal muscles differently, with gene expression changes primarily in metabolism and stress response. All muscles showed distinct RNA profiles but shared common pathways for repair and oxidative metabolism.
Area of Science:
- Immunology
- Molecular Biology
- Skeletal Muscle Physiology
Background:
- Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions.
- The differential impact of MG on various skeletal muscles is not well understood.
- Experimental autoimmune MG (EAMG) in rats serves as a model to study disease mechanisms.
Purpose of the Study:
- To investigate the hypothesis that different skeletal muscles exhibit distinct responses to EAMG.
- To identify common and unique gene expression patterns in extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum longus (EDL) during EAMG.
- To elucidate the molecular mechanisms underlying muscle susceptibility and adaptation in EAMG.
Main Methods:
- EAMG was induced in Lewis rats via immunization with acetylcholine receptor (AChR).
- RNA expression profiling was performed on EOM, DIA, and EDL tissues six weeks post-induction.
- Quantitative PCR (qPCR) was used to validate RNA profiling results.
Main Results:
- 359 probes (1.16% of 31,090) showed >2-fold expression changes between EAMG and control groups.
- Commonly altered genes across muscles were associated with metabolism, stress response, and signaling.
- EAMG induced a shift towards oxidative metabolism and activated genes for muscle regeneration and immune suppression.
Conclusions:
- While each muscle type displayed a unique RNA profile, commonalities in gene expression related to repair, inflammation moderation, and oxidative metabolism were observed.
- The study did not find evidence of a differential immune response among the examined muscles.
- EAMG significantly alters gene expression in skeletal muscles, promoting oxidative metabolism and activating regenerative pathways.
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