title: Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors--Recommendations for methods and experimental designs.
abstract: Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice.
authors: Division Neuroscience, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. Electronic address: m.losen@maastrichtuniversity.nl.
authors: Mario
authors: M
authors: Losen
authors: Division Neuroscience, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors: Pilar
authors: P
authors: Martinez-Martinez
authors: Division Neuroscience, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors: Peter C
authors: PC
authors: Molenaar
authors: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
authors: Konstantinos
authors: K
authors: Lazaridis
authors: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
authors: Socrates
authors: S
authors: Tzartos
authors: Laboratory of Neuroimmunology, Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Talma
authors: T
authors: Brenner
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, PR China.
authors: Rui-Sheng
authors: RS
authors: Duan
authors: Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA, USA.
authors: Jie
authors: J
authors: Luo
authors: Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA, USA.
authors: Jon
authors: J
authors: Lindstrom
authors: Department of Pharmacology & Physiology, The George Washington University, Washington, DC, USA.
authors: Linda
authors: L
authors: Kusner
mesh_terms: D000818:Animals; D007114:Immunization / Q000379:methods* / Q000592:standards*; D020720:Myasthenia Gravis, Autoimmune, Experimental; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology
chemical_list: D011950:Receptors, Cholinergic
keywords: Acetylcholine receptor; Experimental autoimmune myasthenia gravis; Myasthenia gravis; Rat; Torpedo californica