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Mother's diet changes pups' colour

Mouse study suggests mechanism for affect of maternal nutrition on infant health.

The Agouti gene, that makes mice fat and yellow, is silenced in pups of vitamin-dosed mothers. Credit: © Waterland & Jirtle.

Researchers in the United States have altered the coat colour and disease susceptibility of newborn mice - simply by feeding their mothers extra vitamins during pregnancy1.

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 development.

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 Wolf Reik , Babraham Institute

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 fertilization.

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.


  1. Waterland, R. A. & Jirtle, J. L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Molecular and Cell Biology, 23, 5293 - 5300, (2003).

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  2. DeBaun, M. R. et al. Epigenetic variations of H19 and LIT1 in patients with Beckwith-Weidermann Syndrome with cancer and birth defects. American Journal of Human Genetics, 72, 604 - 611, (2003).

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Murphy, G. Mother's diet changes pups' colour. Nature (2003).

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