Navigation Links
A screening strategy using zebrafish targets genes that protect against hearing loss

A small striped fish is helping scientists understand what makes people susceptible to a common form of hearing loss, although, in this case, its not the fishs ears that are of interest. In a study published on February 29 in the open-access journal PLoS Genetics, researchers at the University of Washington have developed a research method that relies on a zebrafishs lateral linethe faint line running down each side of a fish that enables it to sense its surroundingsto quickly screen for genes and chemical compounds that protect against hearing loss from some medications. The study was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health.

The fishs lateral line contains sensory cells that are functionally similar to those found in the inner ear, except these are on the surface of the fishs body, making them more easily accessible, said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. This means that scientists can very efficiently analyze the sensory structures under different conditions to find out what is likely to cause damage to these structures and, conversely, what can protect them from damage.

When people are exposed to some antibiotics and chemotherapy agents, the sensory structures in the inner ear, called hair cells, can be irreversibly damaged, resulting in hearing loss and balance problems. These are known as ototoxic medications. People vary widely in their susceptibility to these agents as well as to damage caused by other chemical agents, loud sounds and aging.

To find out why this is so, senior scientists Edwin Rubel, David Raible, and their research team developed a screening strategy that uses hair cells in the lateral line of zebrafish larvae to signal how hair cells in a persons inner ear might respond under similar conditions. Hair cells are named for small bristly extensions, or stereocilia, jutting from their tops. Movement of fluid (triggered by sound vibrations in the inner ear or changes in water pressure in the fishs environment) causes the stereocilia to tilt to one side, generating an electrical impulse that travels to the brain.

The researchers first set out to identify genes that may be involved in how hair cells respond to ototoxic medicines. Using a chemical that causes random mutations in zebrafish, the researchers bred various fish families, with each family exhibiting a different set of mutations. The researchers then exposed five-day-old larval offspring to the drug neomycin, a type of antibiotic that damages these hair cells as well as those in the human inner ear. The larvae were then stained to determine if the hair cells were still intact. Fish that were resistant to damage were quickly identified as were those that were especially vulnerable.

Using genetic techniques, the group then examined the larvaes DNA, searching for segments that were closely tied to the desired property. In doing so, they zoomed in on five mutationseach located on different genesthat, when inherited from each parent, protected against hair cell damage. Further examination revealed that one of the identified genes corresponds to a gene that is also found in other vertebrates, including humans. Another five mutations were identified that offer protection under more complex genetic conditions.

Next, the team investigated whether they could identify chemical compounds that protect hair cells against ototoxic medicines. Using the same screening techniqueexposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cellsthe researchers screened more than 10,000 compounds and narrowed them down to two similar chemicals that provide robust protection of hair cells against the neomycin. One of the compounds was later found to protect hair cells from a mouses inner ear against the drug, indicating that the same compound may be protective for other mammals as well.

One of the pluses about working with zebrafish is that, like other fish, they produce hundreds of offspring. We can look at lots of animals and we can look at many hair cells per animal, which means that we can get good quantitative data, said Dr. Raible.

The authors suggest that their research technique, which combines chemical screening with traditional genetic approaches, offers a fast and efficient way to identify potential drugs and drug targets that may one day provide therapies for people with hearing loss and balance disorders.


Contact: Mary Kohut
Public Library of Science

Related biology news :

1. UNC study questions FDA genetic-screening guidelines for cancer drug
2. MIT: Micro livers could aid drug screening
3. New screening strategy for detection of chagas disease in children
4. Simple screening questionnaire for kidney disease outperforms current clinical practice guidelines
5. Embryonic stem cell strategy advanced with UCSF finding
6. Penn Veterinary Medicine report new strategy to create genetically-modified animals
7. Bee strategy helps servers run more sweetly
8. Lupus Research Institute strategy delivers $30 million in national funding
9. Texas Hospital nations first to use large-scale cocoon strategy against whooping cough
10. Carbon capture strategy could lead to emission-free cars
11. Strategy for nanotechnology-related environmental, health and safety research
Post Your Comments:
(Date:11/10/2015)... Nov. 10, 2015  In this report, ... basis of product, type, application, disease indication, ... this report are consumables, services, software. The ... safety biomarkers, efficacy biomarkers, and validation biomarkers. ... are diagnostics development, drug discovery and development, ...
(Date:11/9/2015)... , Nov. 9, 2015  Synaptics Inc. (NASDAQ: ... today announced broader entry into the automotive market with ... match the pace of consumer electronics human interface innovation. ... are ideal for the automotive industry and will be ... Europe , Japan ...
(Date:10/29/2015)... Minn. , Oct. 29, 2015   MedNet ... supports the entire spectrum of clinical research, is pleased ... Minnesota High Tech Association (MHTA) as one of only ... in the "Software – Small and Growing" category. The Tekne ... individuals who have shown superior technology innovation and leadership. ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... , November 24, 2015 ... new market research report "Oligonucleotide Synthesis Market by Product ... (PCR, Gene Synthesis, Diagnostic, DNA, RNAi), End-User (Research, Pharmaceutical ... published by MarketsandMarkets, the market is expected to reach ... in 2015, at a CAGR of 10.1% during the ...
(Date:11/24/2015)... SHPG ) announced today that Jeff Poulton , Chief ... Annual Healthcare Conference in New York City , ... p.m. GMT). --> SHPG ) announced today that ... Jaffray 27 th Annual Healthcare Conference in New ... 8:30 a.m. EST (1:30 p.m. GMT). --> Shire plc ...
(Date:11/24/2015)... CITY , Nov. 24, 2015 /PRNewswire/ - ... "Company") announced today that the remaining 11,000 post-share ... Share Purchase Warrants (the "Series B Warrants") subject ... were exercised on November 23, 2015, which will ... Shares.  After giving effect to the issuance of ...
(Date:11/24/2015)... ... November 24, 2015 , ... InSphero AG, the leading supplier of easy-to-use solutions ... Melanie Aregger to serve as Chief Operating Officer. , Having joined InSphero ... team and was promoted to Head of InSphero Diagnostics in 2014. There ...
Breaking Biology Technology: