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 The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>