title: Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental Autoimmune Myasthenia Gravis in Rats.
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 theTorpedo. 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.
authors.affiliation: Department of Neurology, George Washington University Washington, DC, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaminski
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Himuro
authors.affiliation: Department of Neurology, George Washington University Washington, DC, USA.
authors.forename: Jumana
authors.initials: J
authors.lastname: Alshaikh
authors.affiliation: Department of Pediatrics, Washington University St. Louis, MO, USA.
authors.forename: Bendi
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Pathobiology, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Georgiana
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Pharmacology and Physiology, George Washington University Washington, DC, USA.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Kusner
keywords: acetylcholine receptor; autoimmunity; gene expression profiles; metabolism; myasthenia gravis; skeletal muscle