Featured Research

from universities, journals, and other organizations

Zebrafish Provide Useful Screening Tool For Genes, Drugs That Protect Against Hearing Loss

Date:
March 4, 2008
Source:
NIH/National Institute on Deafness and Other Communication Disorders
Summary:
Scientists have developed a research method that relies on a zebrafish's lateral line -- the faint line running down each side of a fish that enables it to sense its surroundings -- to quickly screen for genes and chemical compounds that protect against hearing loss from some medications.

A small striped fish is helping scientists understand what makes people susceptible to a common form of hearing loss, although, in this case, it's not the fish's ears that are of interest. In a new study researchers at the University of Washington have developed a research method that relies on a zebrafish's lateral line -- the faint line running down each side of a fish that enables it to sense its surroundings -- to quickly screen for genes and chemical compounds that protect against hearing loss from some medications.

"The fish's lateral line contains sensory cells that are functionally similar to those found in the inner ear, except these are on the surface of the fish's 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 person's 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 fish's 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 larvae's DNA, searching for segments that were closely tied to the desired property. In doing so, they zoomed in on five mutations--each located on different genes--that, 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 technique--exposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cells--the 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 mouse's 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.

Journal reference: Owens KN, Santos F, Roberts B, Linbo T, Coffin AB, et al. (2008) Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death. PLoS Genet 4(2): e1000020. doi:10.1371/journal.pgen.1000020

*The study was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health. Other sponsors of the study include the American Academy of Otolaryngology--Head and Neck Surgery Foundation, the University of Washington Royalty Research Fund and the V.M. Bloedel Hearing Research Center.


Story Source:

The above story is based on materials provided by NIH/National Institute on Deafness and Other Communication Disorders. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute on Deafness and Other Communication Disorders. "Zebrafish Provide Useful Screening Tool For Genes, Drugs That Protect Against Hearing Loss." ScienceDaily. ScienceDaily, 4 March 2008. <www.sciencedaily.com/releases/2008/02/080229153115.htm>.
NIH/National Institute on Deafness and Other Communication Disorders. (2008, March 4). Zebrafish Provide Useful Screening Tool For Genes, Drugs That Protect Against Hearing Loss. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2008/02/080229153115.htm
NIH/National Institute on Deafness and Other Communication Disorders. "Zebrafish Provide Useful Screening Tool For Genes, Drugs That Protect Against Hearing Loss." ScienceDaily. www.sciencedaily.com/releases/2008/02/080229153115.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Thousands Who Can't Afford Medical Care Flock to Free US Clinic

Thousands Who Can't Afford Medical Care Flock to Free US Clinic

AFP (July 23, 2014) America may be the world’s richest country, but in terms of healthcare, the World Health Organisation ranks it 37th. Thousands turned out for a free clinic run by "Remote Area Medical" with a visit from the Governor of Virginia. Duration: 2:40 Video provided by AFP
Powered by NewsLook.com
Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins