title: From classic to spontaneous and humanized models of multiple sclerosis: impact on understanding pathogenesis and drug development.
abstract: Multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), presents as a complex disease with variable clinical and pathological manifestations, involving different pathogenic pathways. Animal models, particularly experimental autoimmune encephalomyelitis (EAE), have been key to deciphering the pathophysiology of MS, although no single model can recapitulate the complexity and diversity of MS, or can, to date, integrate the diverse pathogenic pathways. Since the first EAE model was introduced decades ago, multiple classic (induced), spontaneous, and humanized EAE models have been developed, each recapitulating particular aspects of MS pathogenesis. The advances in technologies of genetic ablation and transgenesis in mice of C57BL/6J background and the development of myelin-oligodendrocyte glycoprotein (MOG)-induced EAE in C57BL/6J mice yielded several spontaneous and humanized EAE models, and resulted in a plethora of EAE models in which the role of specific genes or cell populations could be precisely interrogated, towards modeling specific pathways of MS pathogenesis/regulation in MS. Collectively, the numerous studies on the different EAE models contributed immensely to our basic understanding of cellular and molecular pathways in MS pathogenesis as well as to the development of therapeutic agents: several drugs available today as disease modifying treatments were developed from direct studies on EAE models, and many others were tested or validated in EAE. In this review, we discuss the contribution of major classic, spontaneous, and humanized EAE models to our understanding of MS pathophysiology and to insights leading to devising current and future therapies for this disease.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, 234 Herzl St. Rehovot, 7610001, Israel. Electronic address: avi.ben-nun@weizmann.ac.il.
authors.forename: Avraham
authors.initials: A
authors.lastname: Ben-Nun
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, 234 Herzl St. Rehovot, 7610001, Israel. Electronic address: nathali.kaushansky@weizmann.ac.il.
authors.forename: Nathali
authors.initials: N
authors.lastname: Kaushansky
authors.affiliation: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried 82152, Germany; Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, 81377 Munich, Germany. Electronic address: Naoto.Kawakami@med.uni-muenchen.de.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawakami
authors.affiliation: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried 82152, Germany. Electronic address: guru@neuro.mpg.de.
authors.forename: Gurumoorthy
authors.initials: G
authors.lastname: Krishnamoorthy
authors.affiliation: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried 82152, Germany. Electronic address: berer@neuro.mpg.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Berer
authors.affiliation: INSERM, U1043, Toulouse, F-31300, France. Electronic address: roland.liblau@inserm.fr.
authors.forename: Roland
authors.initials: R
authors.lastname: Liblau
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, 81377 Munich, Germany. Electronic address: Reinhard.Hohlfeld@med.uni-muenchen.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.affiliation: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried 82152, Germany. Electronic address: hwekerle@neuro.mpg.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity
chemical_list: C571326:MOG protein, human; C571327:Mog protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Antigen-based immune-specific therapy; Experimental autoimmune encephlalomyelitis (EAE); HLA-II transgenic mice; Humanized EAE models; Multiple sclerosis (MS); Spontaneous EAE models