Thou shall have a fishy on a little dishy, thou shall have a fishy when the 3Rs boats come in

Kulkarni P, Yellanki S, Medishetti R, Sriram D, Saxena U, Yogeeswari P. Novel Zebrafish EAE model: A quick in vivo screen for multiple sclerosis. Mult Scler Relat Disord. 2017 Jan;11:32-39. doi: 10.1016/j.msard.2016.11.010.


Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators.


The EAE model was developed by disease induction with myelin oligodendrocyte glycoprotein – 35-55 (MOG) and observation of survival, clinical signs and body weight changes. We have validated this model using fingolimod. We have further performed detailed validation using dimethyl fumarate, dexamethasone and SR1001, which are known modulators of rodent EAE.


The immunization dose for the disease induction was observed to be 0.6mg/ml of MOG in CFA (Complete Freund’s adjuvant), injected subcutaneously (s.c.) near spinal vertebrae. In the validation study with fingolimod, we have demonstrated the modulation of disease symptoms, which were also confirmed by histopathological evaluation. Furthermore, detailed validation with three other known drugs showed that our observations concur with those reported in conventional rodent models.


We have standardized and validated the adult zebrafish EAE model. This model can help get a quick idea of in vivo activity of drugs in a week using very low quantities of candidate compounds. Further work will be required to define this model particularly as it is found that zebrafish may not express a MOG homologue.

  • Zebrafish develop EAE
  • Zebrafish EAE is treated with MS DMT
  • You don’t need to use mice, or larger animals, to look for Immunosuppressive treatments
  • Another nail in the rodent EAE coffin?
  • If this work is true, and it needs to be repeated, the authors lucked out

As anyone who works on animals in the EU, you are committed to consider the 3Rs (refinement, reduction replacement) of animals in research. 

People take the argument for using mice because there is no other less sentient animal to do the study.

This rug is being pulled from under the carpet and if this work proves to be true, it could set the cat amongst the pigeons.

Zebrafish are one of the model organisms that people use because the offspring are transparent and you can make transgenic ,gene-altered fish. There are quite a few myelination projects going on in these fish.

However, this study says you can get EAE in fish, by immunizing them with myelin peptides just like you would do in a mouse.

Is this the end of mouse EAE,. Maybe if the ethics committee eat this study up.

However, is it true?

It will be repeated and I guess this will be starting today or tomorrow being monday

The authors started by injecting myelin oligodendrocyte glycoprotein (MOG) in adjuvant to induce a paralytic disease.  So far so good but as the fish do not produce MOG, how can this occur? There is no target to be attacked by the immune system.

Next they used fingolimod, which traps T (& B) cells in lymph glands so they can’t get in the blood so thet can’t get in the brain. However, fish don’t have lmyph glands, but fingolimod blocks the EAE. How can that be?

The study “smells fishy

This could mean it is all tosh, but maybe it is a lucky study.

The simple solution is for someone else to repeat it, but this takes fishy studies into a new level of ethics

Studies in the mouse report that immune responses to the MOG peptide can cross react with a immune responses to a nerve protein to induce the disease? Does this operate here? We don’t know because there were no T cell responses measured.

This will mean repeating the work, but this may be another signal for killing off those EAE, that are justified in the name of MS research, that have so little real relevance.

I get that bad Home office (Animal Inspectors) feeling coming .

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