Why do Two Genetically Identical Mice Look Vastly Different?

Let's start with a study of mice by

Randy Jirtle. I understand these are

known as Agouti Mice. Is is this

something from the High Andes the Agouti

Mice what does Agouti mean, and why

why is this study that you did now so

often cited as being important for

understanding epigenomics?
- So Agouti just

means Brown.
-- oh
-- it's not not too exciting

so you have two mice, I call these the

Agouti sisters so from the hot dutch

study and the Chinese famine studies, you

knew that something occurring very early

in development, literally in the

first trimester of development,

ultimately gave rise to increased

susceptibility to diseases, including

cardiovascular disease, obesity, diabetes

and a doubling or tripling of the

incidence of schizophrenia. So severe

lack of nutrition early in development

results in all of these disease

characteristics 20-30 years later. The

real problem though was what, is the

mechanism by which the glue, the gravity,

the molecular mechanism that holds these

two disparate time points together. And

this is how this study, why this study is

so important. So the only difference

between the brown mouse and the yellow

mouse on this slide is what the mother

was exposed to when they were in utero.

these are genetically identical mice. the

mother on the left, the yellow mouse, that

mother was just eating normal Mouse Chow.

the mother on the left was eating mouse

chow that was supplemented with things

like folic acid, choline, etc. Why those

compounds? Because they're the ones that

provide the methyl groups that are

placed down onto the DNA all those

methyl groups that are needed for

programming come in from our diet. So

that's why this early time point is so

important. So here you have a mouse that

is small, lean and clean, doesn't get

diabetes, doesn't become obese. the only

reason is because what had happened, and

what that offsprings mother ate very

early in development, and what we showed

is, in this system anyway, that that

molecular mechanism that

relates these two time points together

is DNA methylation at a region that's

upstream is Agouti Mouse. So for the

first time we showed that small changes

in nutrition can alter disease

susceptibility, not through alterations

in the genome, but by alterations in the

epigenome and this is fundamental.

-- And one can already imagine the potential

for, I believe we're already in some

courts, legal responsibilities of mothers

-- It's possible I don't get into the legal

aspects. I have enough travel with the

scientific crowd.
--Right, but the work you

all have done is now made this a very

sensible question.
--Exactly and there's

real potential for good from this, if we

can understand how to protect.
-- I like to

think about and focus on the good

aspects of this, rather than the negative

aspects.
-- Right and you have good reason

though to believe that these may be

mechanisms that may be not totally

unlike our own.
-- It looks like from some

of the model genes that we've been

looking, at for example these imprinted

genes, that indeed is the case. You can

see environmental alterations the

epigenome of these regulatory elements