Another Loooooooooooooong Post

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In response to posts on EAE

You wrote “Given that the risk factors for MS in humans are female gender, Vit D deficiency, infection with EBV, smoking, month of birth, how does the mouse model reflect these factors?

In simple language it doesn’t, as the animal model has sufficient risks to develop disease. These risk factors combine to determine if one person or another will get MS. However, in most cases animals strains only represent one individual as they are genetically identical, clones These are selected because they have an inbuilt susceptibility to disease. Furthermore, in animal studies we start from the point of having disease and have a few tricks how we can trigger MS-like disease in animals.


However let’s look at the risk factors you mention

PART 1

Females: The simple reason why there are more females than males that get MS is sex. In most autoimmune disease, where the immune system attacks the body such as rheumatoid arthritis and lupus, more females develop disease than males. The odd-one-out is type I diabetes where the sex ratio of females to males is about the same. However, this is often a disease of children with an onset before puberty, whereas most other autoimmune diseases, such as MS, are often adult-onset diseases occurring after puberty.

Animal studies can clearly link the differences in susceptibility to autoimmunity to the action of sex hormones. In many cases a female to male preponderance to susceptibility can be found, in some cases male mice may be more susceptible. Likewise males mice may develop worse progression when they develop disease, just as can occur in MS.

PART II

Vitamin D Deficiency and Latitude and Month of Birth. These are probably linked to sunshine which makes Vitamin D in humans. You get less sunshine the further North (in UK) you live and if you are born in May your mum got less sunshire whilst you are in the womb. This lack of vitamin D may shape how your immune system develops. This may then influence whether your immune system attacks your own nerves, which is MS.

In contrast to humans, mice are active during the night and stay our of the sunshine in case they get eaten. They also have a the gestation period of 3 weeks , from conception to birth, compared to 9 months in humans. Therefore the evolutionary pressures are very different but rest assurred vitamins play a role in the immune system of rodents (rats and mice).

My old boss was working in New York, but when he came back to London he couldn’t get the experiment to work. Turned out the answer was vitamins and so every week the animals used to get cabbage…they loved it….and the experiments started to work. Likewise we can show how vitamin D influences the immune response in mice.

PART III

Epstein Barr Virus is a virus that doesn’t infect rodents (rats and mice) and so to study this you would need to use monkeys. However animal studies can given us ideas of how infections can help trigger MS.and only recently you may remember that infection of a colony of Japanese Monkeys with an EBV-like virus caused a very MS-like disease.

“Just so you know there are no places in the United Kingdom that undertakes studies in monkeys in relation to MS”.

However, because we know that infections have the potential to influence outcomes in experiments we spend much of our time ensuring that animals used in research are free of infections. Therefore animals are often kept in specialised animal facilities with equipment that filter-out infections.

If they do get in, such as via humans bringing them into the animal units, a lot of resource is required to get rid of the infections. One way is treatment with drugs, but it may mean a more radical approach. As infections do not cross the placenta between mum and babies, we have to perform a c-section just before birth, revive the pups and foster them onto infection-free mums. I have helped deliver many mouse pups in my time.

PART IV

Smoking. Fortunately animals don’t smoke. However, because smoking is considered a social evil, alot is known about smoking and risks of disease. I suspect we willl soon be collecting information on booze, TV and online gambling, mobile phones and computers

“We all know that ice cream consumption goes up when it is hot outside! It is hot outside because the sun is out! The suns gives off ultraviolet radiation that induces a sun tan! Ultraviolet radiation can induce damage to DNA! DNA breaks can lead to influences on dividing cells! Uncontrolled division of cells can give rise to give cancer! Therefore ice cream causes cancer?

Well maybe the above is abit far fetched, but we know that smoking increases the risk of MS, just as it can protect you from some neurodegenerative diseases. Is this because of smoke? Is it because of nicotine? Is it because smokers exhibit a behaviour that is the risk factor? We know that females are smoking more and they have a higher risk of MS.

Well the simple answer is there is much to learn. Some answers we can seek through using animals, other aspects are much better done in humans.

I am sure Prof. G will keep you all informed about risk factors

PART V

One more risk factor is Genetics. There are many genetic factors that increase the risk of developing MS, but one in particular is linked to the development of MS. This is the major histocompatibility complex (target for DNA fingerprints) that controls how immune responses are generated.This also determines if you would reject an organ transplant. In mice if you have certain variants of the major histocompatibility complex you may get EAE and others you will not. However if we take a disease-resistant mouse and engineer it so that the only difference is that it has a major histocompatibility complex comes from the susceptible mouse, then it gets disease.

The point of all of the above is that we start with the examing the human disease. We only use animals to address simple questions that help us to better understand the human condition, when we can not get the information from studying the disease.

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