Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

Discovering the Missing "LINC" to Deafness

29.01.2013
Mutation in a genetic protein prevents hearing, reports a TAU researcher

Because half of all instances of hearing loss are linked to genetic mutations, advanced gene research is an invaluable tool for uncovering causes of deafness — and one of the biggest hopes for the development of new therapies.


The different position of cell nuclei in unhealthy (red) cells relative to healthy (blue) cells leads to deafness.

Now Prof. Karen Avraham of the Sackler Faculty of Medicine at Tel Aviv University has discovered a significant mutation in a LINC family protein — part of the cells of the inner ear — that could lead to new treatments for hearing disorders.

Her team of researchers, including Dr. Henning Horn and Profs. Colin Stewart and Brian Burke of the Institute of Medical Biology at A*STAR in Singapore, discovered that the mutation causes chaos in a cell's anatomy. The cell nucleus, which contains our entire DNA, moves to the top of the cell rather than being anchored to the bottom, its normal place.
Though this has little impact on the functioning of most of the body's cells, it's devastating for the cells responsible for hearing, explains Prof. Avraham. "The position of the nucleus is important for receiving the electrical signals that determine proper hearing," she explains. "Without the ability to receive these signals correctly, the entire cascade of hearing fails."

This discovery, recently reported in the Journal of Clinical Investigation, may be a starting point for the development of new therapies. In the meantime, the research could lead towards work on a drug that is able to mimic the mutated protein's anchoring function, and restore hearing in some cases, she suggests.

From human to lab to mouse

Prof. Avraham originally uncovered the genetic mutation while attempting to explain the cause of deafness in two families of Iraqi Jewish descent. For generations, members of these families had been suffering from hearing loss, but the medical cause remained a mystery. Using deep genetic sequencing, a technology used to sequence the entire human genome, she discovered that the hearing impaired members of both families had a mutated version of the protein Nesprin4, a part of the LINC group of proteins that links the cell's nucleus to the inner wall of the cell.

In the lab, Prof. Avraham recreated this phenomenon by engineering the mutation in single cells. With the mutation in place, Nesprin4 was not found in the area around the cell nucleus, as in healthy cells, but was spread throughout the entire cell. Investigating further, she studied lab mice that were engineered to be completely devoid of the protein.

Created in Singapore, the mice were originally engineered to study the biology of LINC proteins. The fact that they were deaf came as a complete surprise to researchers. Without this protein serving as an anchor, the cell nucleus is not located in the correct position within inner ear cells, but seems to float throughout. This causes the cells' other components to reorient as well, ultimately harming the polarity of the cells and hindering electrical signals. It's a mutation that took a heavy toll on the cells' ability to transfer sound signals, explains Prof. Avraham, rendering the mice deaf.

Given the similarity between mouse and human inner ear cells, researchers predict that the same phenomenon is occurring in human patients with a mutation in the Nesprin4 gene.

Looking for a wider impact

Prof. Avraham says that she and her collaborators are the first to reveal this mutation as a cause of deafness. "Now that we have reported it, scientists around the world can test for mutations in this gene," she notes. The mutation could indeed be a more common genetic cause of deafness in a number of populations. And because Nesprin4 belongs to a family of proteins that have been linked to other diseases, such as muscular coordination and degeneration disorders, this could prove a ripe area for further research.

At TAU, the research was supported by the National Institutes of Health — NIDCD and Israeli Center of Research Excellence, I-CORE.

G. Hunka | EurekAlert!
Further information:
http://www.aftau.org

More articles from Health and Medicine:

nachricht Stopping HIV in its tracks
28.04.2015 | Oak Crest Institute of Science

nachricht Women show persistent memory impairment after concussion
28.04.2015 | Radiological Society of North America

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: Komponisten liefern Erklärung für Hawaii-Knick

Von Hawaii bis nach Kamtschatka zieht sich eine Kette von größtenteils unter Wasser liegenden, erloschenen Vulkanen durch den Pazifik. Diese Hawaii-Emperor-Kette ist die Spur eines vulkanischen Hotspots. Doch warum ändert sie auf halbem Weg die Richtung?

Ein internationales Forscherteam unter Beteiligung des GEOMAR Helmholtz-Zentrums für Ozeanforschung Kiel, des Alfred-Wegener-Institut, Helmholtz-Zentrum für...

Im Focus: Ist unser Universum ein Hologramm?

Zur Beschreibung des Universums braucht man möglicherweise eine Dimension weniger als es den Anschein hat. Rechnungen der TU Wien legen nun nahe, dass es sich dabei nicht bloß um einen Rechentrick handelt, sondern um eine grundlegende Eigenschaft des Raums.

Auf den ersten Blick scheint jeder Zweifel ausgeschlossen: Das Universum sieht für uns dreidimensional aus. Doch eine der fruchtbarsten Ideen der theoretischen...

Im Focus: Hummelgenom entschlüsselt

Eine Kollaboration von Forschenden unter ETH-Federführung hat das Genom von zwei kommerziell bedeutenden Hummelarten aufgeklärt. Die Resultate bieten unerwartete Einblicke in Ökologie und Evolution der Hummeln und auch der Honigbiene.

Hummeln gelten als friedfertig und fleissig. Nicht zuletzt seit es weltweit mit der Honigbiene bergab geht, ist der kommerzielle Wert dieser Insekten...

Im Focus: Elektromobilität: Ultraleichtes Kraftpaket für das elektrische Fliegen

Siemens hat einen einzigartigen Elektromotor entwickelt, der hohe Leistung mit einem minimalen Gewicht kombiniert. Durch konsequente Optimierung aller Komponenten stellt der neue Antrieb in seiner Klasse einen Weltrekord beim Leistungsgewicht auf. Dadurch kommt der routinemäßige Einsatz von elektrisch angetriebenen Flugzeugen oder Helikoptern einen großen Schritt näher.

Manchmal lässt sich eine technische Revolution ganz knapp in einer einzigen Zahl zusammenfassen. In diesem Fall lautet sie: fünf Kilowatt pro Kilogramm – das...

Im Focus: Fast and Accurate 3-D Imaging Technique to Track Optically-Trapped Particles

KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.

Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

MS Wissenschaft - Leinen los und durch Berlin

28.04.2015 | Veranstaltungen

Internationale Mathematik-Konferenz

28.04.2015 | Veranstaltungen

Biomass to Power and Heat - Tagung am 6. und 7. Mai 2015 an der Hochschule Zittau/Görlitz

28.04.2015 | Veranstaltungen

 
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Siemens eröffnet neuen Standort der Geschäftseinheit eCar Powertrain Systems

28.04.2015 | Unternehmensmeldung

Fraunhofer-Institut erhält den GreenTec Award für ressourcenschonende Dämmung

28.04.2015 | Förderungen Preise

Schaumstoffe aus Holz

28.04.2015 | Förderungen Preise