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 Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>