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Deafness and seizures result when mysterious protein deleted in mice
Date:1/24/2008

ission.

In the current study, published in the Jan. 24, 2008 issue of Neuron, the team explored the role of VGLUT3 in mice genetically engineered to lack the transporter. The effect was dramatic.

Mice lacking the transporter are completely deaf from birth, says the senior author of the study, Robert Edwards, MD, professor of neurology and physiology at University of California, San Francisco. Moreover, they had significant seizures.

As the gene that encodes VGLUT3 is known to have sequence variations in humans, it is possible that these or other variations may be the underlying cause of deafness or epilepsy in humans, according to the researchers. They plan to screen people with these conditions for variations in the vglut3 gene, says the first author of the study, Rebecca Seal, PhD, a postdoctoral fellow in the Edwards laboratory

In addition, because the mice in the study lacked the protein in all cells that would normally make it, the team plans to make a conditional knockout, in which the gene is inactivated only in specific types of nerve cells. This will reveal which nerve cells expressing VGLUT3 account for a particular brain function.

At the outset of the study, the team knew that VGLUT3 was expressed during brain development by a population of inhibitory GABAergic neurons in the brainstem pathway that transmits information about sound. They suspected that the absence of VGLUT3 -- which would allow the release of the excitatory glutamate -- might produce a subtle defect in sound localization. Instead, the animals were completely deaf.

The explanation, they learned, was that VGLUT3 contributes to the release of glutamate at a key point in the production of sound. It turns out that inner hair cells of the cochlea, which are known to convert the auditory input, or signal, into glutamate release, express VGLUT3, and the transporter contributes to the release of glutamate onto the first neuron in the pathwa
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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