Dumb animals

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Dumb animals

Postby JFH » Fri Dec 03, 2004 1:46 am

I'm sure someone here will know!

Does any form of MS occur naturally in any mammal other than hom. sap. ? If not why not? If so ... sidestep animals rights debates John :?
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Postby BioDocFL » Fri Dec 03, 2004 8:39 am

There is a paper out this month (I think it was one of the Nature journals) that compares the EAE model in mice to MS and they found there were some similarities in EAE and MS in the active genes versus normal humans. Whether they are pertinent genes to the disorder, I don't know if the authors could show that. Sorry I didn't keep that citation handy. It was in one of these eTOCs (electronic table of contents) that I get each month. Usually (especially Nature) I can only see the abstracts.
Something I have mentioned before are two mouse strains, Quaking and Jimpy, which I believe are good models of neurodegeneration. I think this is closer to what is occurring in MS lesion sites before any autoimmune inflammation develops. The work I saw was circa 1975 and I haven't noticed any other references to these mice in MS research more recently. I think the bias is against using these mice since it doesn't model the autoimmune aspects. I referenced the articles in the forum>general discussion>polyamines.
Other than those two points, I don't know enough about animal models of MS to give you any further information yea or nay.
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Postby cdaw » Fri Dec 03, 2004 4:31 pm

Is EAE naturally occuring, or is it only induced in the lab?
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Postby BioDocFL » Fri Dec 03, 2004 5:29 pm

You're right about EAE, it's induced. I didn't read the original question closely enough. Here is a quick description of EAE:


http://www.mult-sclerosis.org/experimen ... litis.html

'Experimental Autoimmune Encephalomyelitis (EAE), also called Experimental Allergic Encephalomyelitis, is an animal model of Multiple Sclerosis. Animal models of human diseases are diseases of non-human species (often rodents) which closely resemble their human counterparts and are be studied with a view to better understanding and treating the human form. EAE is not multiple sclerosis, nor is it a single disease in a single species, but its different forms resemble the various forms and stages of MS very closely in a large number of ways.
EAE is an acute or chronic-relapsing, acquired, inflammatory and demyelinating autoimmune disease. The animals are injected with the whole or parts of various proteins that make up myelin, the insulating sheath that surrounds nerve cells (neurons). These proteins induce an autoimmune response in the animals - that is the animal's immune system mounts an attack on its own myelin as a result of exposure to the injection. The animals develop a disease process that closely resembles MS in humans.
EAE has been induced in a number of different animal species including mice, rats, guinea pigs, rabbits, macaques, rhesus monkeys and marmosets. For various reasons including the number of immunological tools, the availability, lifespan and fecundity of the animals and the resemblance of the induced disease to MS, mice and rats are the most commonly used species.
The animals are in-bred to reliably produce susceptibility to EAE in the animals. As with humans and MS, not all mice or rats will have a natural propensity to acquire EAE. Moreover, different breeds will develop different forms of EAE, some of which act as good models for the different human forms of MS. Different EAE forms are also used as models for the different stages of MS.
Several proteins or parts of proteins (antigens) are used to induce EAE including: Myelin Basic Protein (MBP), Proteolipid Protein (PLP), and Myelin Oligodendrocyte Glycoprotein (MOG).
Researching EAE has a number of benefits:
Because EAE is an animal disease, it enables researchers (especially immunologists) to study demyelination (the process underlying the symptoms of MS) in ways that would not be morally acceptable in studies of MS in humans.
It allows researchers to test potential treatments for MS for their efficacy and safety without putting the lives of people at risk.
It allows researchers to experiment with different ways of inducing EAE to attempt to find potential causes of MS.
Because the generations times of most of the EAE species are short, and because they breed very fast, large populations of such animals can be turned over in short periods of time.
Researching EAE has a number of disadvantages:
EAE is not multiple sclerosis and a number of significant assumptions are made when proposing EAE as an animal model for MS.
It is undeniable that the animals involved suffer considerably - at the very least they are given the animal equivalent of MS - and questions about the ethics of EAE are inescapable.
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Postby HarryZ » Fri Dec 03, 2004 6:36 pm

Wesley,

If one reads Dr. P. Behan's Pathogenisis of MS, he comes out and states that MS in mice isn't anything like MS in humans. That, he says, is the main reason why there has never been a treatment that has worked in the mouse that has worked in humans.

He does say that the EAE model in mice is a great tool for following the disease in a labratory but that's about as far as it goes.

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Postby BioDocFL » Fri Dec 03, 2004 9:45 pm

HarryZ

Yes, from what little I have read about the EAE model, it doesn't appear to match MS well enough. It apparently can mimick some of the immunology but, as we have been discussing in other topics, the immune activity may not be the starting point of MS. So perhaps adopting EAE as a model means that one is adopting an immune system driven theory for MS, without stating that bias. As far as the recent paper citing gene similarities between EAE and MS, I cited another paper in another topic comparing MS, lupus, and normal. Approximately half the genes in MS versus controls matched lupus versus control genes. I wonder if EAE even compared that well to MS. I've got to get those papers and read them in detail. Oh, and the MS, lupus, normal comparisons were made with peripheral blood cells so that really doesn't address what might be occurring in an MS lesion.
I did some searching on Google but could not find any other animal models of MS, just variations on EAE induction (MBP, MOG, hepatitis virus) and the species in which it is induced (mice, rabbits, monkeys). And there don't appear to be any naturally occurring incidents of MS in other species than humans.
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