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Missing gene a potential risk factor for birth defects

Mouse embryos missing a gene that aids in the repair of DNA damage are at greater risk of developing birth defects, say University of Toronto scientists. The finding has implications for research into the cause of birth defects in humans.

The gene, also found in humans, produces an important protein called ATM which senses DNA damage caused by reactive oxygen species and directs other proteins to repair it. Reactive oxygen species are a normal product of the body's production of energy but can jump to toxic levels when cells are exposed to certain drugs, environmental chemicals and agents such as ionizing radiation.

In a study published online by the FASEB Journal in March, researchers at U of T's Leslie Dan Faculty of Pharmacy found that mice embryos genetically engineered to lack one or both copies of the ATM gene and then exposed to ionizing radiation and a subsequent overload of reactive oxygen species were at increased risk for dying in utero, developing birth defects or experiencing other developmental problems after birth. Because the mice lacked the protection of the ATM protein, these problems occurred even though the level of radiation was far below that which would normally affect a developing embryo.

"Although these pathways have not been investigated in the human embryo, these findings in mice provide new insights into how the embryo protects itself from oxidative stress and the associated risk factors for embryonic death and abnormal development," says senior author Professor Peter Wells. "This research provides evidence that the ATM gene protects embryos from birth defects initiated by DNA damage. In fact, when this gene is missing in mice, even without exposure to drugs, the normal physiological production of reactive oxygen species can be enough to damage the embryo. The next step is to see if this holds true for humans."

The prevalence of humans missing one copy of the ATM gene is relatively common, around one to t
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Contact: Jessica Whiteside
jessica.whiteside@utoronto.ca
416-978-5948
University of Toronto
31-Mar-2004


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