Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps research scientists identify genetic cause for type of deafness

07.09.2009
Discovery could lead to new therapies for progressive hearing loss

A team led by scientists from The Scripps Research Institute has discovered a genetic cause of progressive hearing loss. The findings will help scientists better understand the nature of age-related decline in hearing and may lead to new therapies to prevent or treat the condition.

The findings were published the September 3, 2009, in an advance, online issue of the American Journal of Human Genetics, a publication of Cell Press.

"It is thought that mutations in several hundred genes can lead to deafness," said team leader Ulrich Mueller, a professor in the Department of Cell Biology and member of the Skaggs Institute for Chemical Biology at Scripps Research. "However, for many forms of deafness, we don't know what effects the genes have. In this new research, we have linked a previously uncharacterized gene to deafness, first in mice and then in humans."

The team found that the gene responsible for the hearing loss—called Loxhd1—is necessary for maintaining proper functioning hair cells in the inner ear. Mutations in Loxhd1 lead to degradation of the hair cells and a disruption of the process that enables hearing.

Tracking Down a New Gene

In the new study, members of the Mueller lab used a technique called forward genetics in their quest to better understand the genetic basis of hearing and hearing loss.

In forward genetics, scientists make mutations at random in germ cells, screen the resulting models for physical characteristics of interest (in this case hearing impairment), then amplify these traits through the breeding of several generations. The gene responsible for the trait is then identified through positional cloning.

In this case, the scientists were able to generate a new mouse line with hearing impairment that they called samba and then clone the gene responsible, Loxhd1, which had never before been associated with deficits in hearing. When the mice inherited two copies of the mutated gene, they were profoundly deaf shortly after birth.

The scientists' next task was to determine why.

Normally, "hair cells" or stereocilia in the inner ear respond to fluid motion or fluid pressure changes caused by sound waves that enter the outer ear, travel down the ear canal into the middle ear, then strike the eardrum, which vibrates and moves a set of delicate bones that communicate with the inner ear. There, the movement of the stereocilia transmits signals to sensory neurons, sending signals to the brain and eventually resulting in hearing.

The scientists found that mutations in the Loxhd1 gene did not appear to affect the initial development of the stereocilia. However, these mutations did impair the function and maintenance of these essential structures, eventually leading to their degradation and to hearing loss.

But one essential question remained—was there a parallel gene in humans that also caused hearing impairment?

To find out, the Mueller lab reached out to Professor Richard J. H. Smith, the Sterba Hearing Research Professor at Carver College of Medicine, Iowa State University. Smith had been spearheading an effort to collect DNA samples from deaf families for years, and had hundreds of groups of samples in which to search for Loxhd1. Indeed, when the analysis was completed, the team found that mutations in the Loxhd1 gene were present in some of these families with hearing loss.

Clues to Age-Related Deafness

This is the third hearing-related gene that the Mueller lab has discovered, and one he is particularly excited about.

"In humans, the prevailing difficulty is progressive hearing loss," he said. "As you age, you lose your hearing slowly. Since this mutation can lead to progressive hearing loss, it provides us with more information on the genetic underpinnings of this condition and gives us clues as to how it might be corrected."

Mueller's lab is currently investigating the possibility that a therapeutic drug could be effective in reversing the molecular problems that result from the defective gene.

The first authors of the paper, "Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans," are Nicolas Grillet and Martin Schwander of Scripps Research.

In addition to Mueller, Smith, Grillet, and Schwander, authors of the paper include: Michael S. Hildebrand of the University of Iowa City; Anna Sczaniecka, Anand Kolatkar, and Peter Kuhn of Scripps Research; Janice Velasco of the Translational Genomics Research Institute; Jennifer A. Webster, Kimia Kahrizi, and Hossein Najmabadi of the University of Social Welfare and Rehabilitation, Iran; William J. Kimberling of the Boys Town National Research Hospital; Dietrich Stephan of the Genome Institute of the Novartis Research Foundation, Arizona Alzheimer's Consortium and Banner Alzheimer's Institute; Melanie Bahlo of The Walter and Eliza Hall Institute of Medical Research, Australia; and Tim Wiltshire and Lisa M. Tarantino of the University of North Carolina, Chapel Hill.

The research was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health and the Skaggs Institute for Chemical Biology, as well as a fellowship from the Bruce Ford and Anne Smith Bundy Foundation, an Australian National Health and Medical Research Council (NHMRC) Career Development Award, and a NHMRC Overseas Biomedical Fellowship.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. The Scripps Florida campus is in Jupiter, Florida.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht The world's tiniest first responders
21.06.2018 | University of Southern California

nachricht A new toxin in Cholera bacteria discovered by scientists in Umeå
21.06.2018 | Schwedischer Forschungsrat - The Swedish Research Council

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Better model of water under extreme conditions could aid understanding of Earth's mantle

21.06.2018 | Earth Sciences

What are the effects of coral reef marine protected areas?

21.06.2018 | Life Sciences

The Janus head of the South Asian monsoon

21.06.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>