Jax Labs eBook - 12

IMPACTFUL SOLUTIONS CREATE INNOVATIVE SCIENCE

You also have physical issues,
especially in motor neuron diseases,
where we are asking for motor neurons to
transverse the whole area of our bodies
and mice are very small creatures. And,
they are crawling around on all fours
where we are putting a lot of pressure as
uprights. So, there are differences that we
have to be careful of.
When people say, "Well, how come
there are no good mouse models for ALS"
or "How come there are no good mouse
models for Alzheimer's," I would say that
that is not a true statement. I think that
there are good mouse models; they are
just not simple.
I think as scientists, especially as
geneticists-in the past, we focused on
those phenotypes that had really good
penetrance and that were a little bit
simpler to dissect. Now we are having
to start putting our heads together
about how we model these complex
diseases.

12 | GENengnews.com

FISHER: I would like to add to that,
because this is something I feel quite
strongly about working in the ALS field. I
think that anybody who works with mouse
models to try to understand human
disease, before they go anywhere near
a mouse, has to ask: what do I want this
model to tell me?
One example is ALS, which is 90%
sporadic, meaning we don't really know
why it arises, but about 10% of it is
familial. Of that 10%, there are at least 25
different genes that when mutated give
absolutely bang-on monogenic Mendelian
inherited, usually as an autosomal
dominant ALS.
Given that, if you are trying to study
ALS, you need to be very clear which
genetic model is going to answer the
question you wish to address, and I cannot
tell you the number of times where people
have come up to me and asked, "What
is the best model for ALS?" And the first
question to throw back is, "Well, which
type of ALS? It is not one single disease,

so which model do you want to work with?
Is it going to be one of the RNA binding
proteins or is it going to be a superoxide
dismutase-1 model?" Particularly for
people who are thinking about translation,
you have to really think about what it is
you want to model and then go to the right
mouse.
There is not a one-size-fits-all
because it is biology and biology is very
subtle. We need to get the message
out there that mice are great for
understanding mechanism. They can be
very, very good indeed for translation,
but it is up to the individual researcher to
understand their model and understand
what it can tell them.
BOGDANIK: The challenge moved from
creating new models, to phenotyping
them. Back when genetic engineering
was made with ES-cells, there were few
models and a large community would
work with them: steadily, huge amount of
information would be collectively gathered


http://www.GENengnews.com

Jax Labs eBook

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