Navigation Links
Zebrafish provide useful screening tool for genes, drugs that protect against hearing loss
Date:2/29/2008

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 in the Feb. 29 issue of the 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. Such medications are called ototoxic. 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, Ph.D., David Raible, Ph.D. 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: Jennifer Wenger
jwenger@mail.nih.gov
301-496-7243
NIH/National Institute on Deafness and Other Communication Disorders
Source:Eurekalert

Related medicine news :

1. Phylonix granted broad European patent for transplanting human cells into zebrafish
2. Transparent zebrafish help researchers track breast cancer
3. NIH awards Phylonix phase II SBIR to develop zebrafish models for eye diseases
4. Microbiotic technology developed for microinjection of zebrafish embryos
5. Johnson & Johnson Diabetes Institute, LLC Launches New Center to Provide State-of-the-Art Education, Training to Health Professionals
6. Crdentia Selected by Leading Staffing Vendor to Provide Health Care Staffing Services to One of the Largest Hospital Chains in the U.S.
7. Hooper Holmes to Provide Business Update
8. XCPT(TM) Patient Engagement and Communication Software and DentalXP.com, a Leading Provider of Online Dental Education and Content, Sign a Co-Marketing Agreement
9. AMN Healthcare Reports Fourth Quarter and Year End 2007 Results; Provides Full Year 2008 Guidance
10. HASP Online Provides Free Job Safety Analysis Tool Available Online
11. Microsoft to Showcase Innovative Solutions for Healthcare Providers and Consumers at HIMSS 2008 Annual Conference & Exhibition
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/10/2016)... ... February 10, 2016 , ... Everseat has joined the ... available to physicians. The integration will enable Allscripts users to post open appointments ... free mobile app. , The partnership gives Everseat substantial added power to help ...
(Date:2/10/2016)... Jacksonville, Florida (PRWEB) , ... ... ... of North Florida – 1 UNF Drive, Jacksonville, FL 32224, February 26th: ... $30, February 27th: Elite Division - Time: 7:00pm – 10:00pm | Ticket ...
(Date:2/10/2016)... ... 2016 , ... Workrite Ergonomics, who is celebrating their 25th year of business ... being an internationally recognized leader in their industry. , "We are very proud of ... of Workrite. “Workrite recognized the importance of good ergonomics before most of our ...
(Date:2/10/2016)... ... , ... Anxiety of older Americans over steep cost increases of prescription drugs ... ago, according to The Senior Citizens League (TSCL). Since last fall, ... rapidly rising costs. “The implications are chilling, particularly for people with chronic health ...
(Date:2/10/2016)... Puente, California (PRWEB) , ... February 09, 2016 ... ... Medicine students, faculty and staff helped give free oral screenings to 150 children ... Feb. 5, 2016. , The College of Dental Medicine joined Chinese American Dental ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... ATLANTA , Feb. 10, 2016  LexisNexis® ... and technology, today announced the launch of ... analytics solution that helps improve and optimize the ... evaluation of performance using severity-adjusted scores. By measuring ... a critical solution to deliver better outcomes, improve ...
(Date:2/10/2016)... VIEW, Calif. , Feb. 10, 2016 ... of a synergistic confluence of various technologies ... value propositions, previously unavailable. These opportunities create ... and convergence, in turn, drives the development ... entrepreneurial scenario is characterized by technology convergences, ...
(Date:2/10/2016)... Mast Therapeutics, Inc. (NYSE MKT: ... sickle cell disease and heart failure, today announced the ... at a price to the public of $0.275 per ... Company,s common stock and one warrant to purchase one ... price of $0.42 per share. The warrants are exercisable ...
Breaking Medicine Technology: