EAE Mouse Models of Multiple Sclerosis (MS)

Q: What is the "EAE Score"?

The EAE Scoring System is a standardized clinical scoring system that assesses the disease progression in this rodent model. It typically uses a 5 point scale. There are several variations on the EAE score, and we would be happy to discuss what may be most suitable for your study.

Q: What is the typical dosing paradigm?

The dosing paradigm can be: (1) Prophylactic (starting before or at the time of immunization) (2) Therapeutic/interventional (a) Starting when the first mice show symptoms (b) Starting from the first signs of symptoms in each mouse (c) Starting a fixed time after immunization or symptom onset in each mouse Our team can discuss the best dosing paradigm for your study.

Q: Can a "positive control" be included in the study?

Yes. The existence of well-established positive controls is an advantage of the EAE animal models.

Q: What is the difference between using MOG35-55 and MOG1-125?

The MOG1-125 induced model is thought to have some dependence on B cells, which may be useful for evaluating B cell-targeted therapies.

Q: What is the difference between active and passive EAE models?

In active EAE, the disease is induced in mice via immunization with myelin-derived antigens, such as MOG, PLP, or MBP. MOG35-55-induced EAE is commonly used to induce EAE in C57BL/6 mice, making is a well-established and widely employed rodent model for studying autoimmune demyelinating diseases. In passive EAE (also known as adoptive transfer), the disease is induced by first generating encephalitogenic CD4+ T cells that are specific for myelin-derived antigens in immunized (donor) mice, then activated these cells in culture, and finally injecting them into recipient mice. This approach is useful when therapies target specific T cell populations.

Q: Can Biospective perform "adoptive transfer" (passive) EAE model studies?

Yes. We can generate these animal models and our EAE model scientists would be happy to discuss further with you.

Q: Is neurofilament light a useful measure in EAE?

Definitely. Blood (plasma or serum) and/or CSF neurofilament light chain (NfL; NF-L) concentrations are excellent measures of axonal damage in this mouse model of multiple sclerosis. You can learn more about the use of neurofilament light chain as a marker of axonal damage and axon degeneration in our Resource - Experimental Autoimmune Encephalomyelitis (EAE) & Axonal Injury.

EAE Model Overview

Experimental Autoimmune Encephalomyelitis (EAE) is a widely-used animal model for assessing therapeutic agents targeting autoimmune-mediated central nervous system (CNS) disease. EAE induction is most commonly performed by immunizing mice against myelin-derived antigens, such as:

Myelin Oligodendrocyte Glycoprotein (MOG_35-55 or MOG_1-125)
Myelin Basic Protein (MBP)
Proteolipid Protein (PLP)

EAE mice model several key aspects of human MS, including the following key pathologic features:

Neuroinflammation (activated microglia & reactive astrocytes)
Peripheral inflammatory infiltrates (lymphocytes, macrophages)
Demyelination in white matter tracts
Axonal injury/damage & axon degeneration (Read More in our Resource - Experimental Autoimmune Encephalomyelitis & Axonal Injury)

The EAE model of multiple sclerosis demonstrates motor symptoms, such as paralysis, which recapitulates clinical symptoms seen in MS patients. The EAE animal model is characterized by a progressive paralysis followed by full or partial recovery, which may then be relapsing-remitting or chronic depending on the specific antigen used.

EAE Mouse Model Generation

We most frequently use the MOG_35-55 (MOG EAE) model in C57BL/6 mice, which is a well-established, chronic model of multiple sclerosis that is advantageous for therapeutic studies
Injection of MOG_35-55 peptide with Complete Freund's Adjuvant (CFA) and pertussis toxin (PTx) on a defined schedule to produce a T cell-mediated autoimmune disease

Our Validated EAE Mouse Model Measures

Body weight
EAE scores
Grip strength test
Neurofilament light chain measures in plasma & CSF (see Axonal Injury in EAE)
Immunohistochemistry & multiplex immunofluorescence for myelin, peripheral inflammation (e.g. T cells, macrophages), microglia ,and astrocytes in the spinal cord

EAE scoring performed on the MOG_35-55 EAE C57BL/6 mouse model. Note the significantly attenuated disease in the positive control group of mice, which nicely demonstrates the ability to show disease modification in this MS model.