October 14, 2014

Neuronal culprit in genetic disease

A particular neuronal cell population is involved in the pathogenesis of a rare neurological disorder, Vanderbilt researchers have discovered.

(Wellcome Images)

The rare neurological disorder ACCPN is characterized by progressive sensory and motor neuropathy and mental retardation. The disorder has been linked to mutations in the gene encoding the potassium-chloride cotransporter KCC3, a protein that moves ions across the cell membrane.

In previous studies, Eric Delpire, Ph.D., and colleagues disrupted the KCC3 gene in mice and found that the mice had severe locomotor deficits similar to those suffered by patients with ACCPN. Now, Jinlong Ding and Delpire have specifically deleted KCC3 in certain populations of cells to understand the cellular pathology of the disease.

They report in the Nov. 1 issue of Behavioural Brain Research that loss of KCC3 in parvalbumin-positive neurons causes significant motor deficits in mice. Deletion of KCC3 in other cell populations, including certain pain-sensing neurons and Schwann cells that produce myelin coating, did not cause motor deficits. The findings establish the parvalbumin-positive neuronal population – with cell bodies residing in the peripheral dorsal root ganglia – as an important player in the pathogenic development of ACCPN.

This research was supported by grants from the National Institutes of Health (NS036758, GM074771, CA068485, DK059637).

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