Jax Labs eBook - 10


Catherine's case, modeling Alzheimer's
disease, to put them onto these different
strains and then to look at the differences
in phenotype. So, a single mutation,
looking at the difference in phenotype that
arises from that patchwork of different
genes and the genetic backgrounds is a
fantastic way of starting to model genetic
complexity and its outcomes.
Of course, environment is everything.
Environment and how it relates to
phenotype is what happened to your
grandparents, whether your grandparents
were stressed, whether you were stressed
in utero, what you were fed, what kind
of microbiome you have, as Cat alluded
to-everything that we can think about
being human and mouse. Who is in your
cage with you? Do they have the same
mutation as you? Do you actually like that
person who is sharing a cage with you?
All of that will impact on phenotype and
all of that we can model in mice.
However, and this is a challenge for
all of us working with mice in the future,
10 | GENengnews.com

what we now have to get used to is doing
a lot more reporting of how we keep our
mice so the other labs will be able to
reproduce what we do. And an example
of this, which probably none of us would
actually think to put in our papers when
we write up, is do you keep your mutants
in one box together or do you keep them
with wild type controls, because that
will impact on phenotype. But none of
us report it. So, there is an enormously
bright future with mouse models; we
can really drill into what it means to be
human, but we have to report exactly how
we are keeping our animals.
LEMIEUX: Of course, we have to talk
about the emergence of CRISPR. What
impact would you say CRISPR has had
(and will have) in the creation of useful
mouse models for neurobiology research?
FISHER: Well, I think that we haven't yet
really worked out the power of CRISPR.
I think we are going to be able to make

a whole load of changes, not just to the
DNA but also to the epigenome and to
regulate genes in ways that we probably
haven't yet even thought of. Where we
are at the moment is just a snapshot and
not where we are going to be in even five
years' time.
The power of it is that allows us
to address what does it mean to be
human. What if we tweak a single base
pair to modulate a response of a gene
a megabase away? There is just so
much that we can do with it. It allows us
to drill into what is the effect of those
core components of what it means to
be human: luck, aging, phenotype and
LUTZ: Yes, I think that is a great
answer, Lizzie. From the level of
the creation of mouse models, the
technology is relatively easy to use and it
has been adopted by many laboratories,
if not most individual universities. It is
not like the days of targeted mutagenesis


Jax Labs eBook

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