Jax Labs eBook - 8


different environmental exposures in our
experiments. As individuals, we are not
raised in the controlled environments of
cages. We are exposed to a number of
different things throughout our lifetime,
including different bacterial strains and
different viruses, some of which live
within our bodies for our entire life, albeit
sometimes in a dormant phase. And then,
of course, there is the microbiome.
As we start to think about complex
diseases that are the result of an
environmental component as well, as
Lizzie said-the idiopathic diseases-
there may be an easy to see genetic
underlying component. But, we have to
understand the complexity of those things
that are not genetic. And I think we are in
an interesting phase in science right now
to be able to think about tackling those
BOGDANIK: Detailed reporting of the
environment and history of test subjects is
becoming more and more important; drug
8 | GENengnews.com

developers have become very savvy about
mouse models and the way preclinical
studies are designed has changed a lot in
the past few years.
First, in what is expected from
a mouse model: increasingly, the
community recognizes that a detailed
natural history of the model is
needed to design the best protocols;
this means knowing when different
phenotypes appear, how variable they
are from animal to animal, or from one
experimenter to another experimenter,
if they change overtime, if there are
phenotypes not expected from the clinical
presentation in humans, yet making the
mouse model, while valuable, a bit more
complex to work with, etc.
Second, the choice of the tests used
for the natural history and drug efficacy
studies is changing too; for instance,
non-specific assays of neuromuscular
health in mice, like the rotarod test,
which can be affected by stress levels,
dysfunction of the brain, the nerves, the

muscles, the sensory organs or even by
general body weight and metabolism,
are replaced by assays that interrogate
specifically the peripheral nerves
or individual muscles, and have the
sensitivity of the tests used in the clinic
to diagnose patients. Both the detailed
natural history and the new generation of
tests, are great improvements in the way
drug efficacy is tested in these models
nowadays - however this comes with
new challenges: we need these new tests
and the natural history to not increase
the difficulty and costs of preclinical
development to the point where they are
simply not used.
LEMIEUX: Before we move on to
discuss the role of the emergence of new
technologies such as CRISPR, I want to
go back briefly to a point you made, Lizzie,
when you spoke about how mice can
represent some of the variability that we
see in humans. Can you unpack what you
mean by that?


Jax Labs eBook

Table of Contents for the Digital Edition of Jax Labs eBook

Jax Labs eBook - 1
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