Animal models for Multiple Sclerosis Flashcards
What is face validity?
Face validity is the degree of descriptive similarity between the symptoms and the behavioral impairments in the animal model and in the human disease.
What is construct validity?
Construct validity is the degree of similarity between the mechanisms underlying behavior in the model. Animal models can mimic the pathology and the symptoms of the disease but not easily the etiology.
What is predictive validity?
Predictive validity refers to the ability of a model to correctly identify the efficacy of a therapeutic strategy.
What is external validity?
External validity is the way results obtained using a particular model can be generalized/applied to and across populations and repeated in another lab or model.
How is MS induced in animal models?
Chemical agents killing oligodendrocytes or transgenes (TCR/BCR) for the inside-out model. Virus infection (Theiler’s virus, Semliki Forest virus), Active immunization (EAE), or passive immunization (transfer of T-cells) for the outside-in model.
How does active induction of EAE work?
An emulsion of antigen (MOG/PLP/MBP) and adjuvant (DAMP) is injected into a mouse.
How does passive induction of EAE work?
Lymph node cells from Active EAE mice are injected into naïve mice (Adoptive transfer).
Why use non-human primates as MS model?
Monkeys are exposed to the same environment as humans.
What is the immunological difference between mice and humans?
Mice have no memory cells.
Why are marmosets used for MS models?
They are born as bone marrow chimeric twins, have a human-like pathogen-educated immune system, are naturally infected with herpesviruses, and have a human-like CNS architecture.
How does EAE in marmosets look?
The naive immunity (CD4+) looks like mouse EAE and the memory immunity (CD8+) looks like human MS. Autoimmunity against myelin is directed against MOG.
What is the pre-immune pathology in the MS brain?
Microglia nodules on degenerating axons and topical swellings (blisters) of myelinated axons in the white matter.
