( ome mice of a common laboratory type ga...)Neurological Disorder Gene Identified,Health

ome mice of a common laboratory type gave birth to offspring with a strange, wobbly gait and light coat color.

The offspring quickly developed signs of severe central nervous system degeneration and peripheral neuropathy and died. The team named the strain pale tremor mice for their lack of normal pigment and the severe trembling they developed soon after birth.

What could explain the mices debilitating symptoms" And could that knowledge be relevant in people with neurological diseases" Clement Y. Chow, the studys lead author and a U-M Ph.D. student in human genetics, pursued answers.

Chow was able to identify the gene involved, called FIG4, and find the mutation responsible for the symptoms in less than three years. Thats a third of the time it might have taken two decades ago, in part because of valuable data from the Human Genome Project, Meisler says.

Meislers research team, which included scientists at the U-M Life Sciences Institute, found that the mutation caused a signaling molecule, called PI(3,5)P2, to be under-produced in both yeast and mice cells. This little-studied signaling molecule was known to be present in yeast cells but has not been well studied in mammals.

The researchers also identified how the loss of normal FIG4 gene function results in disease in the pale tremor mice: Large fluid-filled chambers called vacuoles crowd the nerve cells and disrupt cell processes.

In mice, the peripheral nervous system was most affected. So we decided to ask whether human patients with peripheral neuropathic disease had the same mutation, says Meisler.

The researchers tested 95 patients with Charcot Marie Tooth disorder of unknown cause. In four patients, they found mutations of FIG4, the same gene implicated in the diseased mice. The finding has resulted in a newly identified form of the disease called CMT4J.

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