(mentions CMT) New Mouse Model Aims to Unlock Neurological Disorders

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New Mouse Model Aims to Unlock Neurological Disorders

July/August 2009 By Dublin

http://www.genomeweb.com/proteomics/new-mouse-model-aims-unlock-neurological-dis\

orders

While mice are invaluable tools to study a range of human diseases, their small

size can sometimes belie the huge difficulty researchers face when attempting to

model complex human neurological disorders. Aside from the challenges relating

to the sheer difference in the size of the nerves, the molecular changes that

cause disease in humans are often very hard to mimic. " The strategy that people

are generally using is to generate targeted mutants with a knockout gene and

then just study the effects, " says Koltzenberg, a professor of clinical

neurophysiology at the University College London's Institute of Neurology. " And

while that is often conceptually clearer, it actually doesn't simulate the

situation in humans where you have single amino acid changes often that then

causes a phenotype. "

But a large-scale collaboration between the University College London, the

Medical Research Centre Harwell, the University of Oxford, the University of

London in England, Vrije University in the Netherlands, and The

Laboratory in Maine has made a dent in this problem. Recently, Koltzenberg and

his collaborators unveiled an effective mouse model for the study of nervous

system diseases Charcot-Marie-Tooth and hereditary motor neuropathy. By making a

mutation in a protein called glycyl-tRNA synthetase (GARS), the group created

mice with many of the same symptoms caused by Charcot-Marie-Tooth and hereditary

motor neuropathy. According to the group, this is the first example of

successful breeding of an animal with the GARS mutation.

One of the biggest hurdles they faced during the project was the lack of an

effective means to help analyze how the animal is affected. " If I had a patient

who presents some neurological abnormalities here at my hospital I would be able

to send them to lots of different consultants with different subspecialties in

neurology, but that is something we really don't have for mouse, " Koltzenberg

says. " So what we really need to develop is something like a mouse hospital

where if you have mutant animals you can easily have them analyzed. "

The required breadth of testing is why the collaboration included so many

institutions. " What we face at the moment, both in America and Europe, is that a

lot of funding is going into knocking out every single gene in the mouse so

people can generate mutant mice, but the big problem is that there are

relatively few people around who can analyze these animals, " Koltzenberg says.

" Some of these techniques are very sophisticated and there are very few places

that can do that kind of analysis. And that is a big problem right now, so

getting all the tests lined up so that they can be done efficiently and you can

look at places where you may not see any pathology is a nontrivial challenge. "