Mother's diet changes pups' colourMouse study suggests mechanism for
affect of maternal nutrition on infant health.
4 August 2003
|The Agouti gene, that
makes mice fat and yellow, is silenced in pups
of vitamin-dosed mothers.|
|© Waterland &
Researchers in the United States have altered the
coat colour and disease susceptibility of newborn mice -
simply by feeding their mothers extra vitamins during
The study is the first to find a clear mechanism for
the effect of maternal nutrition on disease development
in mammals without mutating the offspring's genes.
The implications for cloning, nutrition and disease
research are huge, says Rob Waterland of the Duke
University Medical Center in Durham, North Carolina, who
took part in the study. "For decades, there has been
research linking prenatal diet to diseases like
diabetes, obesity and cancer but the explanation was
missing," he says.
Waterland and his colleague Randy Jirtle worked with
Agouti Yellow mice. Members of this strain have an extra
piece of DNA in the Agouti gene, making them obese and
yellow. When fed the vitamin B12, folic acid, choline
and betaine before, during and after pregnancy, the
animals gave birth to thin, brown pups. Control animals'
offspring were fat and yellow.
The nutrients had silenced the Agouti gene, but had
not altered its sequence, Waterland and Jirtle found.
Molecules containing carbon and hydrogen had been
attached to the gene. Cells often use this process,
called DNA methylation, to switch genes on or off during
This study presents a valuable model system and
underlines the influence of outside factors on gene
expression, says geneticist Wolf Reik of the Babraham
Institute in Cambridge, UK. "It highlights the fact that
external events are important," he says.
We need methods for looking at
methylation in human tissues
But extrapolating from mouse to man needs more data
on human methylation, Reik warns. "We need methods for
looking at methylation in human tissues," he says.
What's more, the Agouti mice received 3-20 times their
required daily level of the tested nutrients. Scaled up
to humans, such doses would be huge. "We shouldn't panic
at this stage," Reik jokes.
In humans, about 40% of DNA is methylated - mostly to
de-activate rogue, nomadic DNA elements that lurk
throughout the genome, which can cause disease if left
unchecked. Many genes are also methylated, including the
cancer-causing p16, and a host of 'imprinted'
genes, one copy of which is de-activated after
Imprinting changes are linked with certain cancers,
and with congenital disorders such as Angelman syndrome
and Beckwith-Weidemann syndrome2.
If diet affects the methylation patterns of imprinted
genes, it could play a role in such conditions.