PLP-Induced EAE Mouse Model of Multiple Sclerosis

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Experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal model of multiple sclerosis (MS), as it shares clinical and pathophysiological features to human disease. EAE is classically characterized by CNS inflammation, demyelination, and paralysis. The myelin proteolipid protein (PLP139-151)-induced EAE model is an active form of the disease, with a relapsing/remitting disease course as opposed to an acute disease course as seen in the MOG-induced EAE model.

In this model, EAE is induced in female SJL mice by immunization with PLP139-151 in complete Freund’s adjuvant (CFA) emulsion followed by two-time administration of pertussis toxin (PTX), resulting in the generation and dissemination of autoimmune T cells into the CNS.  Demyelination of neurons within the CNS leads to impaired locomotor function and mirrors symptoms of the human disease. As with multiple sclerosis in humans, the condition in rodents appears in relapsing-remitting cycles and are characterized by loss of nerve conduction and chronic progression of disability.  

The study described below assesses the progression of locomotor dysfunction in mice subjected to EAE to and validated with the immune modulator FTY-720 (fingolimod; Gilenya®) thereby validating this as a multiple sclerosis model (MS model).

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Body weights.The untreated mice showed an increase in body weight throughout the study. The FTY-720 and vehicle treated mice displayed a decrease in body weights following injection of PLP139-151/CFA, which was maintained throughout the study.

Body-weight and clinical scores of untreated, vehicle-treated and FTY720-treated mice in the EAE model.

Average clinical scores over time. Clinical scores were assessed daily beginning on Day 7 and ending on Day 21. Based on the clinical score system, vehicle treated mice showed an increase in impairment severity throughout the course of the study. The FTY-720 treated mice showed a decrease in impairment following drug administration that became statistically significant when compared to vehicle treated mice on days 17-21. Data are mean ± SEM; * p<0.05, **p<0.01 compared to vehicle.

Clinical Scoring: Mice were randomized according to clinical score on Day 7 of the study. Clinical scoring was completed so that each mouse received one score per day. Clinical scores were evaluated using the following scale:

 

Clinical Score Symptoms
0 No clinical signs; normal activity
1 Limp tail or hind limb weakness, but not both
2 Limp tail and hind limb weakness
3 Partial hind limb paralysis
4 Complete hind limb paralysis
5 Moribund state; death by EAE

 

The PLP139-151-induced EAE Multiple Sclerosis Model can be performed in mice or rats. Typical study duration is about 21 days.

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