Models of MS

Experimental Autoimmune Encephalomyelitis (EAE) is the most commonly used model for Multiple Sclerosis (MS). EAE resembles the human disase in many ways. However, based on the heterogeneity of disease course and lesion pathology in MS it is difficult to model all aspects of MS in one animal model. Thus, the availability of different rat strains, immunogens and adjuvants is very valuable since it allows inducing different types of disease and pathologies. In addition to the actively induced models, the CD4+ T cell dependency of the rat EAE models allows for adoptive T cell transfer of autoimmune T cells after ex vivo re-stimulation. For more detailed information on our models, see disease specific information sheets. 

Rat models of MS

EAE resembles the human disease in many ways. However, based on the heterogeneity of disease course and lesion pathology in MS it is difficult to model all aspects of MS in one animal model. Thus, the availability of different rat strains, immunogens and adjuvants is very valuable since it allows inducing different types of disease and pathologies. In addition to the actively induced models, the CD4+ T cell dependency of the rat EAE models allows for adoptive T cell transfer of autoimmune T cells after ex vivo re-stimulation.

 

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Spinal Cord Homogenate Induced EAE

SCH-induced EAE is induced in DA rats with a homogenate of spinal cord from naive animals emulsified in Incomplete Freunds Adjuvant (IFA). SCH-induced EAE is a severe, relapsing and demyelinating encephalomyelitis. Animals with EAE develop ascending flaccid paralysis that initially affects the tail (score 1-2), later involves hind limbs (score 3-6), forelimbs (score 7) and ultimately result in quadriplegia and death (score 8). The disease is CD4+ T cell mediated and dependent on both Th1 and Th17 cells.

In this model, disease is accompanied by demyelination of the CNS as can be assessed by histology at termination. In additon, IL-17 and IFN-g responses from LNs cells can be assayed ex vivo either as estimation on drug efficacy in vitro or prediction of efficacy for selection of lead compounds before in vivo experiments. The CD4+ T cell dependency of this model allows for adoptive T cell transfer following ex vivo stimulation of autoreactive T cells.

MOG1-125 induced EAE

MOG-induced EAE is induced in DA or Lewis rats with protein emulsified in Incomplete Freunds Adjuvant (IFA) or Complete Freunds Adjuvant (CFA) respectively, and are models well suited for studies of immune mechanisms relevant to MS. MOG-induced EAE is a severe and demyelinating encephalomyelitis with a chronic progressive disease course. The disease is CD4+ T cell mediated and dependent on both Th1 and Th17 cells. T cells, B cells and macrophages are recruited to the inflammatory site resulting in demyelination and axonal loss. IL-17 and IFN-g responses from LNs cells can be assayed ex vivo as estimation on drug efficacy in vivo or prediction of efficacy for selection of lead compounds before in vivo experiments. The CD4+ T cell dependency of this model allows for adoptive T cell transfer following ex vivo stimulation of autoreactive T cells.

MBP induced EAE

MBP-induced EAE is induced in Lewis rats with MBP protein emulsified in Complete Freunds Adjuvant (CFA). MBP-induced EAE is a severe encephalomyelitis with an acute monophasic disease course. Disease has an onset around day 8-10 after immunization and experiment can normally be terminated around day 20. In this model, disease is not accompanied by demyelination of the CNS and there is mainly infiltration of T cells in the CNS. The model is thus suitable for studies to assess basic immunological mechanisms in regard to T cell function in autoimmune disease.

 

 

Mouse models of MS

EAE resembles the human disease in many ways. However, based on the heterogeneity of disease course and lesion pathology in MS, it is difficult to model all aspects of MS in one animal model. Thus, the availability of different strains, immunogens and adjuvants is very valuable since it allows for inducing different types of disease and pathologies. For more detailed information on our models, see disease specific information sheets.

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MOG35-55 induced EAE

EAE induced with MOG peptide (35-55) in C57BL/6 mice are the most frequently used model and is a reliable, reproducible and well characterized model. The immunogenic epitope MOG35-55 is emulsified in CFA and injected s.c. followed by two pertussis toxin injections i.p. (d0 and day 2). Mice develop a monophasic EAE with ascending flaccid paralysis around 1-2 weeks after immunization. Myelin-specific T cells are activated in the periphery and migrate into the CNS across the blood-brain-barrier. Upon entry into the CNS, T cells are re-activated by antigen-presenting cells, ultimately resulting in demyelination and axonal cell death. Pertussis toxin has been suggested to modulate the blood-brain barrier.

MOG35-55 induced EAE is a severe monophasic, demyelinating encephalomyelitis with onset after around 1-2 weeks and reaches maximum score a few days later.

In this model, disease is accompanied by demyelination of the CNS, which can be assessed by histology at termination. In addition, recall IL-17 and IFN-g responses from LNs cells can be assayed ex vivo either as a measurement of drug efficacy or prediction of efficacy for selection of lead compounds before in vivo experiment.

PLP induced EAE

Myelin proteolipid protein (PLP) induced EAE in SJL mice results in a relapsing-remitting disease, suitable for studies of efficacy. The encephalogenic peptide aa 139-151 is emulsified in adjuvant and injected s.c. Disease can be boosted with injection of pertussis toxin. Mice develop a relapsing EAE with ascending flaccid paralysis around 1-2 weeks after immunization. Autoreactive T cells are activated in the periphery and migrate into the CNS across the blood-brain-barrier. Upon entry into the CNS, T cells are re-activated by antigen-presenting cells, ultimately resulting in demyelination and axonal cell death. PLP-induced EAE is a severe and demyelinating encephalomyelitis with a relapsing-remitting disease course. The disease is CD4+ T cell mediated and dependent on both Th1 and Th17 cells. T cells, B cells and macrophages are recruited to the inflammatory site resulting in demyelination and axonal loss. IL-17 and IFN-g responses from LNs cells can be assayed ex vivo as estimation of drug efficacy in vivo or prediction of efficacy for selection of lead compounds before in vivo experiment.