title: Guidelines for standard preclinical experiments in the mouse model of myasthenia gravis induced by acetylcholine receptor immunization.
abstract: Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one of the standard animal models. Although numerous compounds have been recently proposed for MG mostly by using the active immunization EAMG model, only a few have been proven to be effective in MG patients. The variability in the experimental design, immunization methods and outcome measurements of pre-clinical EAMG studies make it difficult to interpret the published reports and assess the potential for application to MG patients. In an effort to standardize the active immunization EAMG model, we propose standard procedures for animal care conditions, sampling and randomization of mice, experimental design and outcome measures. Utilization of these standard procedures might improve the power of pre-clinical EAMG experiments and increase the chances for identifying promising novel treatment methods that can be effectively translated into clinical trials for MG.
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Erdem
authors.initials: E
authors.lastname: Tuzun
authors.affiliation: INSERM U974, Paris, France; CNRS UMR 7215, Paris, France; UPMC Univ Paris 6, Paris, France; AIM, Institute of Myology, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Talma
authors.initials: T
authors.lastname: Brenner
authors.affiliation: Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Kusner
authors.affiliation: INSERM U974, Paris, France; CNRS UMR 7215, Paris, France; UPMC Univ Paris 6, Paris, France; AIM, Institute of Myology, Paris, France.
authors.forename: Rozen
authors.initials: R
authors.lastname: Le Panse
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Patras 26504, Greece.
authors.forename: Socrates
authors.initials: S
authors.lastname: Tzartos
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: pchrista@utmb.edu.
authors.forename: Premkumar
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D017408:Guidelines as Topic; D007114:Immunization / Q000379:methods / Q000592:standards*; D051379:Mice; D020720:Myasthenia Gravis, Autoimmune, Experimental; D011950:Receptors, Cholinergic / Q000276:immunology
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic
keywords: Experimental animal model; Myasthenia gravis; Pre-clinical experiments; Standard operating procedures