Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Low Oxygen Levels May Decrease Life-Saving Protein in Spinal Muscular Atrophy

Investigators at Nationwide Children’s Hospital may have discovered a biological explanation for why low levels of oxygen advance spinal muscular atrophy (SMA) symptoms and why breathing treatments help SMA patients live longer. The findings appear in Human Molecular Genetics.*
SMA is a progressive neurodegenerative disease that causes muscle damage and weakness leading to death. Respiratory support is one of the most common treatment options for severe SMA patients since respiratory deficiencies increase as the disease progresses. Clinicians have found that successful oxygen support can allow patients with severe SMA to live longer. However, the biological relationship between SMA symptoms and low oxygen levels isn’t clear.

To better understand this relationship, investigators at Nationwide Children’s Hospital examined gene expression within a mouse model of severe SMA. “We questioned whether low levels of oxygen linked to biological stress is a component of SMA disease progression and whether these low oxygen levels could influence how the SMN2 gene is spliced,” says Dawn Chandler, PhD, principal investigator in the Center for Childhood Cancer and Blood Diseases at The Research Institute at Nationwide Children’s Hospital.

SMA is caused by mutation or deletion of the SMN1 gene that leads to reduced levels of the survival motor neuron protein. Although a duplicate SMN gene exists in humans, SMN2, it only produces low levels of functional protein. This is caused by a splicing error in SMN2 in which exon 7 is predominantly skipped, lowering the amount of template used for protein construction.

Mouse models of severe SMA have shown changes in how genes are differentially spliced and expressed as the disease progresses, especially near end-stages. “One gene that undergoes extreme alteration is Hif3alpha,” says Dr. Chandler. “This is a stress gene that responds to changes in available oxygen in the cellular environment, specifically to decreases in oxygen. This gave us a clue that low levels of oxygen might influence how the SMN2 gene is spliced.”

Upon examining mouse models of severe SMA exposed to low oxygen levels, Dr. Chandler’s team found that SMN2 exon 7 skipping increased within skeletal muscles. When the mice were treated with higher oxygen levels, exon 7 was included more often and the mice showed signs of improved motor function.

“These data correspond with the improvements seen in SMA patients who undergo oxygen treatment,” says Dr. Chandler. “Our findings suggest that respiratory assistance is beneficial in part because it helps prevent periods of low oxygenation that would otherwise increase SMN2 exon 7 skipping and reduce SMN levels.”

Dr. Chandler says daytime indicators that reveal when an SMA patient is experiencing low oxygen levels during sleep may serve as a measure to include SMA patients in earlier respiratory support and therefore improve quality of life or survival.

*Bebee TW, Dominguez CE, Samadzadeh-Tarighat S, Akehurst KL, Chandler DS. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model. Hum Mol Genet. 2012 Jul 20.

Erin Pope | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht When fat cells change their colour
28.10.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Prototype device for measuring graphene-based electromagnetic radiation created

28.10.2016 | Power and Electrical Engineering

Gamma ray camera offers new view on ultra-high energy electrons in plasma

28.10.2016 | Physics and Astronomy

When fat cells change their colour

28.10.2016 | Life Sciences

More VideoLinks >>>