Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Missing gene a potential risk factor for birth defects

01.04.2004


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 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 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. "It’s 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 - you’d be in big trouble, according to our theory in mice. If it’s 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
Further information:
http://www.newsandevents.utoronto.ca/bin5/040331a.asp

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>