title: Characterization of a reproducible rat EAMG model induced with various human acetylcholine receptor domains.
abstract: Myasthenia gravis (MG) is usually caused by antibodies against the muscle acetylcholine receptor (AChR). Experimental autoimmune MG (EAMG) is the animal model of MG, typically induced by immunization of rodents with AChR isolated from the electric organ of Torpedo californica. We have successfully induced EAMG in Lewis rats by immunization with the extracellular domains (ECDs) of the human AChR subunits (α, β, γ, δ and ε) expressed in yeast. Analysis of the antibody titers revealed a robust antigenic response against all the peptides, but a marked difference in their pathogenicity; the α subunit ECD was the most pathogenic, resulting in the highest percentage of affected animals. Measurements of antibody titers, electromyographic tests and quantitation of the muscle AChR content, offered further support to these findings. The EAMG models presented herein, could be used for studying subunit-specific pathogenic mechanisms, and, more importantly, as tools for the evaluation of antigen-specific therapeutic approaches, which rely on the human AChR.
authors.affiliation: Hellenic Pasteur Institute, GR11521 Athens, Greece. Electronic address: klazaridis@pasteur.gr.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Lazaridis
authors.affiliation: Hellenic Pasteur Institute, GR11521 Athens, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Baltatzidi
authors.affiliation: Hellenic Pasteur Institute, GR11521 Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Trakas
authors.affiliation: Hellenic Pasteur Institute, GR11521 Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Koutroumpi
authors.affiliation: Aiginiteion University Hospital, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Karandreas
authors.affiliation: Hellenic Pasteur Institute, GR11521 Athens, Greece; Department of Pharmacy, University of Patras, Patras, Greece. Electronic address: tzartos@pasteur.gr.
authors.forename: Socrates J
authors.initials: SJ
authors.lastname: Tzartos
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism; D000072417:Protein Domains / Q000502:physiology; D021122:Protein Subunits / Q000276:immunology / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D021122:Protein Subunits; D011950:Receptors, Cholinergic
keywords: Acetylcholine receptor; Animal model; Experimental autoimmune myasthenia gravis; Extracellular domain