Strain of “Pale Tremor” Mice Leads to Gene Discovery

A pale tremor mouse (right) with a normal mouse in Meisler’s lab. Photo: Clement Chow

Thanks to the chance appearance of a strain of mutant mice in their research laboratory, U-M scientists have identified the gene responsible for one type of Charcot-Marie-Tooth disorder, common among inherited neurological diseases.

The discovery means a genetic test will be possible for people with a less common subtype of the disorder — one that until now was unidentified and had an unknown genetic basis, says Miriam Meisler, Ph.D., a professor of human genetics in the Medical School.

It all started when scientists in Meisler’s lab noticed that some mice had offspring with a strange, wobbly gait and light coat color. The team named them “pale tremor” mice. Clement Chow, a Ph.D. student in human genetics, identified a gene mutation called FIG4 that was responsible for the animals’ symptoms.

Large fluid-filled vacuoles pack cells of mice with the FIG4 gene mutation, shown at right, and interfere with cell function. A normal cell is shown at left.

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

Charcot-Marie-Tooth disorder affects one in 2,500 people in the United States. The disease damages peripheral nerves in the feet and legs, causing pain and muscle weakness, foot deformities, and difficulty walking. 

—Anne Rueter

For an expanded version of the story:
www.med.umich.edu/opm/newspage/2007/charcot.htm

For patient information on Charcot-Marie-Tooth:
www.ninds.nih.gov/disorders/charcot_marie_tooth