Duke Study May Push Research Past Gene Mutations
From: Robina Suwol
Date: 05 Aug 2003
Remote Name: 126.96.36.199
Duke study may push research past gene mutations
By Jim Shamp : The Herald-Sun
Jul 31, 2003 : 11:08 pm ET
DURHAM -- Common nutritional supplements given to mice at the Duke
Comprehensive Cancer Center may be feeding a whole new understanding of what
triggers disease and disability.
Duke scientist Randy Jirtle and research fellow Rob Waterland report in
today's issue of Molecular and Cellular Biology that feeding the supplements
to female mice not only changed the color of their mouse offspring's coat, but
also protected them from obesity and related disorders such as diabetes and
It challenges scientists to broaden the way they've been searching for the
origins of disease over the past couple of decades, beyond a focus on gene
mutations. Instead of searching for "the obesity gene" or "the diabetes gene,"
researchers might be finding new answers in patterns of DNA-related activity,
beginning with the first few cells after conception, Waterland said.
He and Jirtle gave mice dietary supplements -- vitamin B12, folic acid,
choline and betaine -- before pregnancy and through lactation. The
supplemented mice had babies predominantly with brown coats. Mice that didn't
get the supplements mostly had babies with yellow coats, even though the
mothers technically weren't deficient in the supplemented nutrients.
The health differences between the different-colored mice, however, were
striking. The scientists found that cellular differences between the groups of
baby mice created the change in coat color, all because the extra nutrients
reduced the expression of a specific gene, called Agouti, which regulates
yellow coat color and obesity. But the gene itself wasn't changed.
"To me, this is really amazing," said Jirtle, professor of radiation oncology
at Duke and the study's senior investigator. "If your mother says eat your
vegetables, do it. This is starting to show that we not only are what we eat,
but we're also what our parents and grandparents ate."
Jirtle said even though it's no surprise that maternal nutrition and other
environmental factors affect babies' health, this study explains for the first
time how they can affect the way genes are expressed, or do their business,
even if those genes remain unchanged.
The color changes in the mouse babies' coats were the result of a process
called "DNA methylation," said Waterland, lead author of the study. That's the
process that appears to involve many other genes that wreak such havoc as
obesity, out-of-control cell growth in cancer, diabetes and possibly even
autism, he said.
During DNA methylation, four atoms -- called a methyl group -- attach
themselves to a gene to alter its function within a cell.
In the treated mice, the researchers said, one or more of the nutritional
supplements caused the Agouti gene to become methylated, changing its ability
to function. It all happened early in the development of the mouse embryos,
Jirtle said, even before pregnancy was apparent.
Nutritional or other environmental effects that early in development can
produce lifelong changes, he said -- including some that can be passed to
future generations. Some of them may be beneficial, he said, like the obesity
protection conferred to the brown mice. Others can be detrimental, such as the
change in the Agouti gene in the yellow mice, which left them unable to
understand when they'd eaten enough. It disabled their internal "satiety
switch," Jirtle said.
"One of the things we need to do now is refine this model and see how
generalizable it is," Waterland said. He noted that he and Jirtle still don't
know which one or combination of the nutritional supplements created the
changes in the experimental mice. They also want to know if other genes might
be involved, and if the supplements caused any negative effects.
"You're going to see more of this kind of work," Jirtle said, "not just from
our group, but from all over."
"At one time, this pursuit, called epigenetic, meaning before genetic, was put
in the same category as metaphysics and pseudoscience by some researchers. But
not anymore. It's real, and it's exciting."
Last changed: March 14, 2006