Shalom Life | April 23, 2014

Discovering the Missing "LINC" to Deafness

Tel Aviv University researcher links hearing loss to genetic protein

By: David Shear

Published: February 4th, 2013 in Health » World

Discovering the Missing "LINC" to Deafness

Did you know that of all the things that cause hearing-loss, half are because of genetic mutations?

For that reason, advanced gene research is an invaluable tool for uncovering causes of deafness — and one of the biggest hopes for the development of new therapies.

And, recently, while researching this phenomenon, a professor at Tel Aviv Universtiy’s Sackler Faculty of Medicine 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.

Prof. Karen Avraham, along with a team of researchers, supported by the National Institutes of Health – NIDCD and Israeli Center of Research Excellence, I-CORE, 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.

"The position of the nucleus is important for receiving the electrical signals that determine proper hearing,” explains \Prof. Avraham. “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.

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.

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.

Israeli Comedian on 4.20: Let My People Smoke! [VIDEO] Israeli Comedian on 4.20: Let My People Smoke! [VIDEO] TrendingEmotional Pain Isn't Just in Your Head Emotional Pain Isn't Just in Your Head TrendingIsraeli Researcher Makes Significant Brain Cancer Discovery Israeli Researcher Makes Significant Brain Cancer Discovery Trending
 

Israeli Wi-Fi Powers Russian Subways

April 22, 2014 | By Daniel Koren
Israeli Wi-Fi Powers Russian Subways

Passengers aboard subways in in Moscow enjoy Wi-Fi courtesy of Israeli communications provider, Radwin

Read More

Israeli Comedian on 4.20: Let My People Smoke! [VIDEO]

April 22, 2014 | By Daniel Koren
Israeli Comedian on 4.20: Let My People Smoke! [VIDEO]

Gadi Wilcherski and a group of Israeli pot advocates campaigned outside Health Minister Yael German's house early Sunday morning

Read More

Shalom, French Polynesia: A Jewish Culture Guide

April 22, 2014 | By Sarah Bauder
Shalom, French Polynesia: A Jewish Culture Guide

Approximately 130 islands comprise French Polynesia, with Tahiti being the most famous, largest, and most populated.

Read More

Katy Perry Impersonates Unfunny Rabbi in ‘Birthday’ Music Video [VIDEO]

April 22, 2014 | By Ashley Baylen
Katy Perry Impersonates Unfunny Rabbi in ‘Birthday’ Music Video [VIDEO]

The pop star takes on a number of the "World's Worst Birthday Party Entertainers"

Read More

Seth Rogen and James Franco to Perform ‘Bound 2’ Spoof at Kim Kardashian Wedding?

April 22, 2014 | By Ashley Baylen
Seth Rogen and James Franco to Perform ‘Bound 2’ Spoof at Kim Kardashian Wedding?

Franco shared some interesting intel about the Kardashian/West wedding on 'The View'.

Read More

Drake to Join Pharrell and Kendrick Lamar at iHeart Radio Music Awards

April 22, 2014 | By Ashley Baylen
Drake to Join Pharrell and Kendrick Lamar at iHeart Radio Music Awards

NBC has announced several big names for iHeart Radio's inaugural event

Read More

David Foster Wallace’s Estate Opposes Upcoming Segel and Eisenberg Biopic

April 22, 2014 | By Ashley Baylen
David Foster Wallace’s Estate Opposes Upcoming Segel and Eisenberg Biopic

Wallace's family and literally trust "have no connection with, and neither endorse nor support" the film entitled 'The End of the Tour'.

Read More

Missouri Mayor Resigns After Siding with Kansas Shooter

April 22, 2014 | By Daniel Koren
Missouri Mayor Resigns After Siding with Kansas Shooter

After saying that he "kind of agreed" with 73-year-old former white supremacist Frazier Glenn Miller, Dan Clevenger has now renounced his position as Mayor of Marionville

Read More

More Headlines