Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Zebrafish to shed light on human mitochondrial diseases

17.09.2007
University of Oregon discovery to benefit studies on COX deficiencies

Zebrafish can now be used to study COX deficiencies in humans, a discovery that gives scientists an unprecedented window to view the earliest stages of mitochondrial impairments that lead to potentially fatal metabolic disorders, according to researchers at the University of Oregon.

COX deficiencies refer to a breakdown of cytochrome coxidase, an enzyme located in the mitochondrion of every cell. Mitochondria are crucial cellular workhorses that provide chemical energy. Research of the deficiency has been stymied by a lack of model organisms, with mice being introduced as the first model by Japanese researchers just seven years ago.

COX involves multiple proteins and assembly factors, and deficiencies of any one of them can negatively affect metabolic tissues, including the brain, muscle and eyes. Deficiencies during the prenatal period are considered to be a potential cause of miscarriages and have been led to prenatal screenings, but scientists still don't understand the metabolic requirements of tissues and organs during early development.

The case for zebrafish (Danio rerio) as an alternative research model is described in a paper posted online ahead of regular publication by the Journal of Biological Chemistry. The comprehensive UO study, led by doctoral student Katrina N. Baden, could speed research and point to specific targets to test potential drug therapies, said co-author Karen Guillemin, a professor of molecular biology and member of the UO Institute of Molecular Biology.

"Mitochondrial impairments are emerging as important in many human diseases, but there have been few models for understanding exactly what is happening during the early development of the diseases," Guillemin said. "The use of mice is limited, because knocking out protein expression in mice mitochondria to mimic human-disease states results in large numbers of deaths in utero. Therefore, the symptoms that researchers have wanted to study have not been assessable in mice."

Baden, a veterinarian, performed several experiments, using RNA-blocking reagents known as morpholinos to reduce gene expression of both a critical COX subunit and Surf1, an assembly-factor protein that when mutated can lead to Leigh syndrome, a severe neurological disorder. She targeted a variety of proteins, alone and in combination, and then added back components to rescue each deficiency. Normal COX activity declined as much as 50 percent in the experimental conditions and resulted in developmental defects in endodermal tissue, cardiac function and swimming behavior in the zebrafish.

"The unique characteristics of zebrafish make them an ideal model for studying the effects of mitochondrial deficiencies on early development," said Baden, who earned her doctorate in July and is now the veterinarian at the UO-based Zebrafish International Resource Center. "Because they develop outside of a uterus and are transparent in early stages, I was able to visualize the effects that molecular alterations have on cell biology, nervous system development, cardiac function and fish behavior."

The external and transparent embryo, Guillemin said, will allow scientists to create specific deficits that mirror those in humans. "The transparency of the embryo will let us see primary defects, what happens in the earliest stages, rather than having to settle for seeing secondary downstream defects later in the disease state," she said.

"Different tissues respond differently to specific losses in mitochondria."

Baden and Guillemin said that the use of zebrafish will improve scientific understanding of the mechanisms of mitochondrial associated pathology in people and speed the identification of new treatments for mitochondrial diseases.

Jim Barlow | EurekAlert!
Further information:
http://www.uoregon.edu

More articles from Studies and Analyses:

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht Do microplastics harbour additional risks by colonization with harmful bacteria?
05.04.2018 | Leibniz-Institut für Ostseeforschung Warnemünde

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
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

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

The dispute about the origins of terahertz photoresponse in graphene results in a draw

25.04.2018 | Physics and Astronomy

Graphene origami as a mechanically tunable plasmonic structure for infrared detection

25.04.2018 | Materials Sciences

First form of therapy for childhood dementia CLN2 developed

25.04.2018 | Studies and Analyses

VideoLinks
Science & Research
Overview of more VideoLinks >>>