Navigation Links
Low oxygen levels may decrease life-saving protein in spinal muscular atrophy
Date:8/21/2012

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.


'/>"/>

Contact: Erin Pope
Erin.Pope@NationwideChildrens.org
614-355-0495
Nationwide Children's Hospital
Source:Eurekalert

Related biology news :

1. Diabetes Research Institute develops oxygen-generating biomaterial
2. Scientists study the catalytic reactions used by plants to split oxygen from water
3. How bacteria change movement direction in response to oxygen: Molecular interactions unravelled
4. PCBs levels down in Norwegian polar bears
5. Growing nitrous oxide levels explained
6. High levels of TRAIL protein in breast milk might contribute to anticancer activity
7. Research!America says house funding levels for FY13 could undermine medical progress
8. Mercury in dolphins: Study compares toxin levels in captive and wild sea mammals
9. Cardio fitness levels of breast cancer patients may affect survival
10. UCSB anthropologists finds high levels of omega-3 fatty acids in breast milk of Amerindian women
11. Increasing levels of carbon dioxide in Arctic coastal seas
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/3/2016)... , February 4, 2016 --> ... SEK 1,351.5 M (105.0), up 1,187% compared with fourth quarter of 2014. ... to SEK 517.6 M (loss: 30.0). Earnings per share increased ... was SEK 537.4 M (neg: 74.7). , ... Revenues amounted to SEK 2,900.5 M (233.6), up 1,142% compared with 2014. ...
(Date:2/3/2016)... -- Vigilant Solutions announces today that the ... solved two recent hit-and-run cases with the ... Solutions. Brian Wenberg explains, "I was ... out of a convenience store and witnessed an elderly male back out ... his vehicle and leaving the scene.  In his statement ...
(Date:2/2/2016)... , Feb. 2, 2016  BioMEMS devices ... primarily focused on medical screening and diagnostic ... parameters. Wearable devices that facilitate and assure ... of movement are being bolstered through new ... biomedical signal acquisition coupled with wireless connectivity ...
Breaking Biology News(10 mins):
(Date:2/11/2016)...  Dovetail Genomics™ LLC today announced that it has ... planned metagenomic genome assembly service. Richard Green , ... method in a talk on Friday, February 12 at ... in Orlando, Fla. ... difficult. Using its proprietary Chicago ™ ...
(Date:2/11/2016)... --  BioInformant announces the February 2016 release of ... Tools, and Technologies – Market Size, Segments, Trends, and ... The first and only market research ... has more than a decade of historical information on ... cell type. This powerful 175 page global strategic report ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... has announced a new agreement with Bankok,Thailand-based Global Stem Cells Network (GSCN) to ... in 15 Latin American countries, including Mexico, Costa Rica, Dominican Republic, Colombia, Argentina, ...
(Date:2/10/2016)... /PRNewswire/ - BioAmber Inc. (NYSE: BIOA ), a ... Mitsui & Co. Ltd., its partner in the ... investing an additional CDN$25 million in the joint venture ... 30% to 40%.  Mitsui will also play a stronger ... Sarnia , providing dedicated resources alongside ...
Breaking Biology Technology: