Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson and Michigan Scientists Identify Gene Defect Behind Muscle-Wasting Disease

13.10.2003


Insights gained from extensive studies in mice may someday lead to treatments for comparable neurodegenerative diseases in humans



Scientists at Jefferson Medical College and the University of Michigan have uncovered a gene defect responsible for a muscle-wasting, neurodegenerative disease in mice known as mnd2. Their results may provide insights into the molecular origins of other such diseases in humans, including Parkinson’s disease.

In an online report on October 8 in the journal Nature, the researchers, led by Emad Alnemri, Ph.D., at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and Miriam Meisler, Ph.D., at the University of Michigan in Ann Arbor, showed that a mutation in a single amino acid in the protein Omi/HtrA2 is enough to cause the neuromuscular disease. In mnd2 mice, the amino acid serine is changed to cysteine.


Michigan senior research associate Julie Jones, a member of Dr. Meisler’s research team, discovered the mnd2 mouse model, an inherited neurological disease, in 1990. mnd2 is characterized by an abnormal gait, muscle wasting and early death. To identify the guilty gene, Dr. Meisler’s laboratory used a technique called positional cloning, eventually narrowing the mutation to a small region containing six candidate genes on chromosome 6. To find the specific genetic defect, they determined the nucleotide sequence of these candidate genes and discovered that the mnd2 defect was caused by a “point” mutation in the Omi gene.

Dr. Alnemri had been studying the Omi/HtrA2 protease – an enzyme that cleaves proteins – and its role in programmed cell death. When he located the Omi gene on chromosome 2p13.1 – which happened to correspond to mouse chromosome 6, where the mnd2 locus is found – he suspected that a mutation in the Omi/HtrA2 gene could be behind the mnd2 disease. According to Dr. Alnemri, who is professor of microbiology and immunology at Jefferson Medical College and a member of Jefferson’s Kimmel Cancer Center, Omi/HtrA2 is present in the mitochondria, which generates energy in the cell. Omi regulates apoptosis, or programmed cell death, by binding and cleaving proteins that block the process. He and his co-workers at Jefferson characterized the mutation and discovered that it causes a loss of proteolytic activity of the protein, though the mutant protease can still bind to apoptosis-blocking proteins.

The Jefferson team performed additional tests on both normal and mutant mice cells, revealing that the cells from mutant mice were more sensitive to cellular stresses. They also discovered that mitochondria are defective in these cells as well. “The normal protease helps maintain normal mitochondrial function and is important for maintaining survival of cells in the nervous system,” says Dr. Alnemri.

The finding was surprising, says Dr. Meisler, a professor in the Department of Human Genetics at Michigan, because “Omi had not been thought to be involved in neurological disease. It appears to cause neuronal cell death by impairment of mitochondrial function.” “Interestingly, that same chromosome region in humans has been mapped in certain patients with Parkinson’s disease,” Dr. Alnemri notes. “We tested a few of these Parkinson’s samples but we did not find mutations in Omi. We still don’t know if this gene is mutated in other types of Parkinson’s or different neurodegenerative disorders.”

“Based on the severe neurodegeneration and muscle wasting in the mnd2 mouse, we will now begin to screen DNA samples from patients with related disorders in order to determine the medical impact of mutations in this gene,” says Dr. Meisler. “The prospects for treatment will be improved by accurate diagnosis in affected patients. We will extend the mutation search to the human gene, in order to determine its role in neuromuscular diseases.”

The Omi protein and related proteins are found in all organisms, including bacteria. In the latter, Omi-related proteins function as “molecular sensors” of cellular stresses, Dr. Alnemri says.

“Our next step is to find out whether Omi in humans functions as a sensor of mitochondrial stress and to understand at the molecular level how Omi regulates mitochondrial function,” he says.

Steven Benowitz | TJUH
Further information:
http://www.jeffersonhospital.org/news/e3front.dll?durki=17158

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

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...

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

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>