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Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain

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Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 26))

Abstract

Modelling complex disorders presents considerable challenges, and multiple sclerosis (MS) is no exception to this rule. The aetiology of MS is unknown, and its pathophysiology is poorly understood. Moreover, the last two decades have witnessed a dramatic revision of the long-held view of MS as an inflammatory demyelinating white matter disease. Instead, it is now regarded as a global central nervous system (CNS) disorder with a neurodegenerative component. Currently, there is no animal model recapitulating MS immunopathogenesis. Available models are based on autoimmune-mediated demyelination, denoted experimental autoimmune encephalomyelitis (EAE ) or virally or chemically induced demyelination. Of these, the EAE model has been the most commonly used. It has been extensively improved since its first description and now exists as a number of variants, including genetically modified and humanized versions. Nonetheless, EAE is a distinct disease, and each variant models only certain facets of MS. Whilst the search for more refined MS models must continue, it is important to further explore where mechanisms underlying EAE provide proof-of-principle for those driving MS pathogenesis. EAE variants generated with the myelin component myelin oligodendrocyte glycoprotein (MOG ) have emerged as the preferred ones, because in this particular variant disease is associated with both T- and B-cell effector mechanisms, together with demyelination. MOG-induced EAE in the non-obese diabetic (NOD) mouse strain exhibits a chronic-relapsing EAE clinical profile and high disease incidence. We describe the generation of this variant, its contribution to the understanding of MS immune and pathogenetic mechanisms and potential for evaluation of candidate therapies.

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Acknowledgments

The work was funded by the National Multiple Sclerosis Society and Novartis Pharmaceuticals Australia. The authors would like to thank LIMS and the Clive and Vera Ramaciotti and Rebecca L. Cooper Medical Research Foundations for equipment. CDS was supported by a post-graduate award from La Trobe University. We also thank A.A. Jimenez for permission to use Fig. 1 and A.A. Ramp for Fig. 2.

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  1. Department of Biochemistry and La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086, Australia

    Phuc T. Dang, Quyen Bui, Claretta S. D’Souza & Jacqueline M. Orian

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Correspondence to Jacqueline M. Orian .

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  1. School of Biological Sciences, Malaghan Institute of Medical Research, Victoria University of Wellington School of Biological Sciences, Wellington, Wellington, New Zealand

    Anne C. La Flamme

  2. Department of Biochemistry, School of Molecular Sciences La Trobe Institute for Molecular Science, Melbourne, Australia

    Jacqueline Monique Orian

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Dang, P.T., Bui, Q., D’Souza, C.S., Orian, J.M. (2015). Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain. In: La Flamme, A., Orian, J. (eds) Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments. Current Topics in Behavioral Neurosciences, vol 26. Springer, Cham. https://doi.org/10.1007/7854_2015_378

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