Increased gene expression of acetylcholine receptor and myogenic factors in passively transferred experimental autoimmune myasthenia gravis.

Abstract

The passive transfer of myasthenia gravis by injection of mAb against muscle acetylcholine receptor (AChR) alpha-subunit, results in increased expression of AChR subunit genes, mainly at synaptic regions. The gene expression of AChR and of other muscle-specific proteins is regulated in a similar manner in passively transferred experimental autoimmune myasthenia gravis (EAMG) and in AChR-induced EAMG. Administration of AChR-specific mAb leads to a significant reduction in muscle AChR content and to an elevation in the mRNA levels corresponding to the adult, synaptic type of the receptor, as shown by Northern blot and in situ hybridization analyses. The mRNA levels of the myogenic factors myogenin and MRF4 are also increased moderately, whereas MyoD transcript levels remain unchanged. Thus, passive transfer of EAMG by mAb directed to defined epitopes of AChR alpha-subunit provides a suitable model for analyzing and following the cascade of molecular events triggered by anti-AChR immunopathologic antibodies and may shed light on the regulatory mechanisms underlying the human disease as well.