Deaf Today: Mutant Mice Speak Out for the Deaf

April 28, 2003

Mutant Mice Speak Out for the Deaf

From: Discovery Channel - Apr 28, 2003

AFP

April 27, 2003 - Experiments with a batch of engineered mice have thrown up exciting genetic clues about why humans often suffer from worsening deafness as they get older.

The evidence points to a rodent gene called Ink4d, which plays a role in sensory hair cells in the inner ear. These cells are the magic behind the so-called Organ of Corti, a structure about four centimetres (two inches) long that spirals along the cochlea and is the vital link in the ability of mammals to hear.

The organ is filled with fluid which moves in response to sound waves.

Thousands of cells with tiny hairs line the organ, and when they move in response to the fluid, they generate electrical signals that stimulate fibres in the auditory nerve which is connected to the brain. This is how we perceive sound.

The problem is that sensory hair cells do not regenerate once they have been lost: the cells carry on dividing until just after a child is born, and then the process abruptly stops.

So if the cells are damaged by loud noise or -- in some individuals -- when the cells die off in significant numbers in later life, the result is progressive hearing loss.

Why these cells do not regenerate may now be explained in part thanks to Ink4d, say researchers at the House Ear Institute in Los Angeles.

Following up evidence that Ink4d plays a role in preventing cells from dividing, the team created mice whose genetic code had been modified to lack this gene.

Sensory hair cells started dividing among adult mice with the deleted gene.

It was not all good news, however: without the restraining influence of Ink4d, the divided cells eventually committed suicide under a process called apoptosis, and the mice became progressively deaf.

The findings are good because they throw up new understanding about progressive hearing loss and tease out fresh ideas about how it may eventually be cured.

It could be, for instance, that an inherited, malfunctioning form of Ink4d could make people more vulnerable to progressive deafness than others. This mutant form of the gene could unleash cell death among sensory hair cells.

The research also throws open the intriguing path of trying to reverse deafness by removing cell-division inhibitors through gene therapy.

That would encourage the cells to grow again, but the apoptosis problem, shown in the mice, shows one of the big hurdles that would lie ahead.

The study is published on Sunday in Nature Cell Biology , a journal of the Nature publishing group.