Missing gene a potential risk factor for birth defects
Research in mice examines how embryo protects itself from oxidative stress
Mouse embryos missing a gene that aids in the repair of DNA damage are at greater risk of developing birth defects, say U of T 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 bodys 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 Ts 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 two per cent of the population, says Wells. There is also a rare condition known as ataxia telangiectasia or AT in which people have no copies of the gene and are highly susceptible to problems such as neurological disorders and cancer.
Not much is known about why some children are more susceptible to birth defects than others, says Wells. If future research found that humans had the same sort of ATM sensitivity as mice, he says, it would suggest the potential for diagnostic tests to determine if an embryo is at risk for birth defects because it lacks the gene and even for possible protein therapies to help counteract ATM deficits in embryos.
"We want to see if the mechanisms that occur in mice will explain what occurs in humans or not," he says. "Its like a Las Vegas slot machine, in reverse. If all the bad lemons lined up - if you had a lot of risk factors, such as no ATM gene combined with exposure to certain drugs and lack of other pathways that protect against reactive oxygen species - youd be in big trouble, according to our theory in mice. If its only a few of the lemons, the risk for developing birth defects or dying in utero would be lower."
The study, by lead author and PhD candidate Rebecca Laposa, was funded by grants and a doctoral award from the Canadian Institutes of Health Research and by a Society of Toxicology fellowship. Other researchers involved in the study were pharmacy professor Jeffrey Henderson and undergraduate student Elaine Xu.
Jessica Whiteside | University of Toronto
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...