Navigation Links
Researchers Have Linked Rett Syndrome to Mitochondrial Gene

Researchers from the laboratory of Adrian Bird, a molecular geneticist at the University of Edinburgh, Scotland, had announced on 23rd June// that the abnormally high levels of a protein called Uqcrc1 in the brains of mouse used as models of Rett Syndrome is causing its mitochondria, which are the powerhouses of the cells to work overtime. Dr. Bird stated that this is the first time that mitochondrial gene has been linked to Rett Syndrome. The co-author of the study Skirmantas Kriaucionis, who is now attached with the Rockefeller University in New York City, hopes that these finding will lead to treatments for the disorder. He said, “Knowledge of specific physiological defects will, in the future, provide targets for therapeutic intervention”. The research, appears in the July issue of the journal Molecular and Cellular Biology, is being funded partly by the Rett Syndrome Research Foundation.

Rett Syndrome (RTT), a devastating neurological disorder, strikes 1 in 10,000 young children, almost all of them girls. In fact, RTT is the leading genetic cause of severe impairment in girls. Symptoms include neuromuscular problems, autonomic dysregulation, seizures and seizure-like episodes, stereotypical hand movements and the inability to speak. Many children are wheelchair-bound, scoliosis is common, and though the majority live to adulthood, they require total care for every aspect of life.

RTT, which is an autism-spectrum disorder, is caused by mutations in a gene called MECP2. Previous research has shown that the protein made by MECP2 is a master controller of other genes, turning them on and off, and scientists have been searching for these genes. Several have been identified, the best known being brain-derived neurotrophic factor, or BDNF, which normally promotes neuronal growth. To find other genes that MECP2 controls, Bird, Kriaucionis, and other colleagues turned to male mice in which MECP2 has been “knocked out”, meaning they lack the prote in completely. These animals are born healthy but begin to walk and breathe abnormally around 6 weeks of age, and start dying off at about 10 weeks (the average lifespan of a mouse is 2 years). The team compared the mutant mice to normal mice in search of genes that were off when they should be on, or vice-versa.

First, Kriaucionis purified the messenger RNA made by about 10,000 different genes from the brains of mutant mice that were almost 10 weeks old. Compared to normal animals of the same age, the team found more RNA produced by seven genes and less RNA made by three. Then Kriaucionis examined the messenger RNA produced by those 10 genes in the brains of mice that had only just started coming down with symptoms, at about 7 to 8 weeks of age. Three of the genes made too much of their protein product in the mutant brains as compared to normal brains.

The team reasoned that these three genes played greater roles in the disorder because they went awry earliest. They decided to focus on Uqcrc1 because much was already known about it, including its role in the mitochondria generating energy.

Mitochondria make energy in four steps, and researchers can test to determine which step malfunctions. The team purified mitochondria from the brains of mice lacking Mecp2 and normal mice. They fed energy precursors to the mitochondria and measured how much energy the factories put out.

Uqcrc1 protein works at the third step in the chain, called complex III. If the researchers supplied precursors that are used by mitochondria before the third step, the mitochondria from the mutant animals made significantly more energy than the normal mitochondria. If they supplied precursors that are used after complex III, the mutant mitochondria made the same amount of energy as normal organelles.

This suggested that overabundance of Uqcrc1 in complex III resulted in mitochondria cranking out more energy than the mutant animals needed . "More sounds better but it isn't necessarily that way," says Bird. "Mitochondria are exquisitely regulated machines, so any deviation from normality is likely to be bad."

To find out if Uqcrc1 was to blame for the mitochondrial defects, the team overproduced the protein in cultured neuronal cells. They isolated mitochondria and repeated the energy production tests. The mitochondria from the cultured cells behaved like the mutant brain mitochondria. "What we wanted to know is if the overexpression of this gene was solely responsible for the overactive mitochondria. And the data said it's likely to be," says Bird. He adds that additional experiments are needed to link the mitochondrial abnormalities to the symptoms found in the mutant mice. The researchers also caution that similar defects need to be looked for in humans.

"Our findings provide a mechanism for how a mutation in MECP2 could result in abnormal mitochondrial function," says Kriaucionis.

"I'm very excited about this paper," says Bruce Cohen, a pediatric neurologist who specializes in mitochondrial diseases at the Cleveland Clinic in Cleveland, Ohio. Dr. Cohen, who did not take part in the work, says it validates the suspicions of a few researchers who have argued that malfunctioning mitochondria play a role in the disorder.

"For over 15 years there have been clinical reports of mitochondrial abnormalities in Rett Syndrome patients. Dr. Bird’s research provides the first genetic link between MECP2 and mitochondria,” states Monica Coenraads, Director of Research for RSRF.

Founded in late 1999, RSRF is the world's largest private source of funds for biomedical research for RTT.

Source: EureAlert

Related medicine news :

1. Researchers urge caution in using ear tube surgery
2. Researchers Scale to assess the Severity of Epilepsy in Kids
3. Researchers trick Alzheimers Enzyme
4. Researchers find new HIV hiding place
5. New Hair in 15 Days Could Now Be A Possibility Say Researchers
6. Researchers developed world’s smallest toothbrus
7. Researchers discover receptor cells that can cause epilepsy
8. 15 Anti-SARS Drugs Identified By China-Europe Team of Researchers
9. Researchers reversed the process of memory loss
10. Researchers Identify Key Gene That May Help Brain Treatment
11. Researchers Discover Protein That Causes Malaria
Post Your Comments:

(Date:12/1/2015)... (PRWEB) , ... December 01, 2015 , ... ... the 1980s we have seen vast improvements in scientific research and discoveries, leading ... strides, providing increased hope and relief to those affected by HIV/AIDS. Mediaplanet’s cross-platform ...
(Date:12/1/2015)... ... December 01, 2015 , ... The importance of volumetric ... the focus of numerous abstracts accepted for presentation here, at the 101st Annual ... abstracts highlight the use of Volpara Solutions’ quantitative breast imaging software tools for ...
(Date:12/1/2015)... ... December 01, 2015 , ... Next ... selected as a finalist in this year’s Fierce Innovation Awards: Healthcare Edition, an ... was recognized as a finalist in the category of Digital Solutions for its ...
(Date:12/1/2015)... ... , ... XTC Semifinals 2016 - CES, Las Vegas, Nevada - ... CES 2016, the world’s largest Consumer Electronic Show, where they will present to a ... of Pacific Investments Veronica Serra, and venture capitalist Tim Draper among many other top ...
(Date:12/1/2015)... ... 2015 , ... SonaCare Medical congratulates the University College London ... on November 18th. This prestigious award recognizes annually organizations that cultivate truly innovative ... medical landscape. , The UCLH team won the award for their innovative approach ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... , December 1, 2015 ... new market research report "Nucleic Acid Labeling Market by ... Nick Translation, Random Primer, In Vitro Transcription, Reverse Transcription, ... published by MarketsandMarkets, The global market is expected to ... Million in 2015, growing at a CAGR of 8.65%. ...
(Date:12/1/2015)... , December 1, 2015 Russia ... clinical trials. 70% of new drugs registered in Europe ... Russia . --> Russia has always been ... of new drugs registered in Europe in 2015 ... --> Russia has always been a country ...
(Date:12/1/2015)... 2015 Relmada Therapeutics, Inc. (OTCQB: RLMD), a clinical-stage ... announced today that the company will present at the LD ... at the Luxe Sunset Boulevard Hotel in Los ... Relmada Therapeutics, will present on Thursday, December 3, at 9:00 ... . Please register at least 10 minutes prior to the ...
Breaking Medicine Technology: