Experiments on mice may aid deaf

Research has identified a gene that is required for proper development of the mouse inner ear, which may help in the understanding of the genetic causes of deafness.

The gene, known as FGF20 in humans, has been associated with inherited deafness in otherwise healthy families.

When the gene was “knocked out” of mice, the animals appeared perfectly healthy but had absolutely no ability to hear.

The FGF20 gene codes for one member of a family of proteins known as fibroblast growth factors. The molecules play key roles in embryonic development, tissue maintenance and wound healing.

Disabling the gene caused a loss of outer hair cells, a special sensory cell in the inner ear responsible for amplifying sound.

Mice lacking FGF20 were missing about two-thirds of their outer hair cells. However, the number of inner hair cells which transmit amplified sound signals to the brain, appeared normal.

Senior author David Ornitz, professor of developmental Biology at Washington University School of Medicine, said: “When we inactivated FGF20 in mice, we saw they were alive and healthy. But then we figured out that they had absolutely no ability to hear.”

The scientists aim to identify the molecular mechanisms that regulate the expression of FGF20 during the embryonic development of the cochlea.

Lead researcher Dr Sung-Ho Huh, added: “This is the first evidence that inner and outer hair cells develop independently of one another.

“This is important because most age-related and noise- induced hearing loss is due to the loss of outer hair cells.”

The researchers speculate that FGF20 signalling will be a required step towards regenerating outer hair cells in mammals, and that this pathway may help them understand how mammals differ from birds and other vertebrates in being incapable of performing such hearing restoration naturally.

Professor Ornitz and his colleagues found that, beyond being a simple “on-off” switch, FGF20 signalling – or its chemical equivalent, FGF9 – must occur on or before day 14 of the embryo’s development to produce a normal inner ear. If it is switched on at day 15, the inner ear fails to develop properly.

This critical “window” may explain why mammals are incapable of regenerating outer hair cells. Whether FGF20 plays a role in this regeneration mechanism remains open to question.

Prof Ornitz and his colleagues also see evidence that mutations in FGF20 may play a role in human deafness, which is another open question currently being investigated.

Previous research has shown that deafness caused by inner ear defects is one of the most common genetic diseases, affecting more than 1 in 1,000 births.