Changes in the expression of mRNAs for myogenic factors and other muscle‐specific proteins in experimental autoimmune myasthenia gravis

Abstract

The regulation of genes for acetylcholine receptor (AChR), myogenic factors and other muscle‐specific proteins has been analyzed in experimental autoimmune myasthenia gravis (EAMG) and following denervation. The levels of the transcripts for the myogenic factors, MyoDl, myogenin and MRF4, were measured using Northern blot analysis. Myogenin and MRF4 transcript levels were observed to be 3.1 ‐ and 2.6‐fold higher in muscle of rats with EAMG than in controls, respectively. MyoDl levels, however, remained unchanged. The increases in AChR, myogenin and MRF4 mRNAs were one order of magnitude higher in 2‐week denervated muscle than in the myasthenic muscle. The levels of muscle creatine kinase (MCK), α‐actin and muscle dystrophin transcripts were also analyzed. Dystrophin levels were found to be 1.7‐ and 4.7‐fold higher in EAMG and denervated muscle, respectively, than in controls; in contrast, MCK and α‐actin levels remained unchanged.

Overexpression of IFN-Induced Protein 10 and Its Receptor CXCR3 in Myasthenia Gravis

“…IL-1␤ was elevated, and TGF-␤ was slightly decreased. As previously reported (18), AChR mRNA levels were up-regulated in the muscles of myasthenic rats.…”

Regulation of acetylcholine receptor gene expression in human myasthenia gravis muscles. Evidences for a compensatory mechanism triggered by receptor loss.

“…However, several arguments indicate that the mechanism involved in the regulation of nAChR expression in human MG differs from that underlying the denervation process: (a) MG is not generally associated with denervation or morphological modifications of motoneuron endings (57) and acetylcholine release at muscle endplates from MG patients is increased (58). (b) We observed no increase in myogenic transcript levels in MG muscles compared to heathly muscles, whereas myogenin, MyoD, and MRF4 mRNA levels are upregulated in denervated models (50,59). (c) The expression of ␥-subunit mRNA was almost undetectable in both healthy and MG muscles, whereas a strong increase in ␥-subunit mRNA levels is observed in denervation models (60).…”

Expression of nerve-regulated genes in muscles of mouse mutants affected by spinal muscular atrophies and muscular dystrophies

“…2 We show here for the mouse that hereditary neuromuscular diseases, especially those with denervation effects (SMAs), lead to drastic up-regulation of the genes for AChR␣ and for the myfs myogenin and MyoD; these diseases also lead to moderate reductions of the muscular chloride channel ClC-1 and parvalbumin mRNAs.…”