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Acetylcholine Receptor-Induced Experimental Myasthenia Gravis: What Have We Learned from Animal Models After Three Decades?

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Myasthenia gravis (MG) is an autoimmune disease caused by an immunological response against the acetylcholine receptor (AChR) at the neuromuscular junction. Anti-AChR antibodies induce degradation of the receptor, activation of complement cascade and destruction of the post-synaptic membrane, resulting in a functional reduction of AChR availability. The pathophysiological role of autoantibodies (auto-Abs) and T helper lymphocytes has been studied in the experimental autoimmune MG (EAMG) models. EAMG models have been employed to investigate the factors involved in the development of MG and to suggest new therapies aimed to preventing or modulating the ongoing disease. EAMG can be induced in susceptible mouse and rat strains, which develop clinical symptoms such as muscular weakness and fatigability, mimicking the human disease. Two major types of EAMG can be induced, passive and active EAMG. Passive transfer MG models, involving the injection of auto-Abs, are helpful for studying the role of complement molecules and their regulatory proteins, which can prevent neuromuscular junction degradation. Active models, induced by immunization, are employed for the analysis of antigen-specific immune responses and their modulation in order to improve disease progression. In this review, we will concentrate on the main pathogenic mechanisms of MG, focusing on recent findings on EAMG experimental models.

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Abbreviations

aa:

Amino acids

AChR:

Acetylcholine receptor

TAChR:

Torpedo californica AChR

auto-Abs:

Autoantibodies

BMSC:

Bone marrow stromal cells

DC:

Dendritic cells

MG:

Myasthenia gravis

MIR:

Main immunogenic region

EAMG:

Experimental autoimmune MG

CFA:

Complete Freund’s adjuvant

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

IgG:

Immunoglobulin G type

MAC:

Membrane attack complex

NMJ:

Neuromuscular junction

PBL:

Peripheral blood lymphocytes

PIX:

Pixantrone (BBR2778)

SCID:

Severe combined immunodeficiency

TGF-β1:

Transforming growth factor 1-beta

Treg:

Regulatory T-cell

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Acknowledgments

We regret that the essential work of many investigators and colleagues could not be included in this review due to space constraints.

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  1. Preclinical Neuroimmunology Laboratory, Neurology IV Unit, Fondazione Istituto Neurologico “Carlo Besta”, Via Celoria, 11, 20133, Milan, Italy

    Fulvio Baggi, Carlo Antozzi, Chiara Toscani & Chiara Cordiglieri

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  1. Fulvio Baggi
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  2. Carlo Antozzi
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Correspondence to Fulvio Baggi.

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Baggi, F., Antozzi, C., Toscani, C. et al. Acetylcholine Receptor-Induced Experimental Myasthenia Gravis: What Have We Learned from Animal Models After Three Decades?. Arch. Immunol. Ther. Exp. 60, 19–30 (2012). https://doi.org/10.1007/s00005-011-0158-6

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