Doctor Thomas Insel makes the case for model animals with the power to see how candidate genes for human disorders could affect other systems.

People ask me a lot about animal models and where are we going with it. I actually don’t like the term. I think the term ‘animal models’ is a misnomer, and it’s probably misguided in the sense that what we’re talking about is not an animal model of schizophrenia or of a mood disorder. I think we’ve chased that for a long time and not gotten very far. We’ve also focused on validating the use of animals with something that looks like schizophrenia or something that looks like depression by saying, ‘If you give the animal an antipsychotic or an antidepressant that the behavior normalizes’. I’m not compelled by that argument either. I think we’re in a different place now, and the different place is that we now for the first time have candidate genes for schizophrenia, for mood disorders, certainly for autism. The power now will be to see what those genes do in other systems, in other organisms. So I would say not animal models as much as we’ll call them model animals, so we’ll be putting these genes into mice, into flies, into fish, into cell systems like embryonic stem cells or this new exciting area of IPS cells; these are cells that come from skin fibroblasts that can be induced to become pluripotent cells and will become a wonderful, I think a really wonderful platform with which to understand how do these changes, often single sequence changes or single base changes in key genes at key times, lead to a change in phenotype? Is that going to give us an animal that will look like it has depression or schizophrenia? Almost certainly not, but what we’re looking for here is trying to understand how these genes play out in the network, in the whole functional pathway and being able to say, ‘Oh look at this, this animal’s pathway of development, the way it forms synapses, the way it develops a synaptic plasticity, the way it forms connections in the developing brain is altered; not everywhere, but in these places and it’s more responsive to an environmental input than it would be otherwise.’ Those kinds of insights, that’s what’s going to drive the next 5 to 10 years, all dependent on (a) having the candidate genes and (b) using model animals as a system in which to find out what are those genes doing?

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