"With such severe muscle atrophy we expected to see a loss of nerve connections on the muscles, but they are all there, and they look relatively healthy," said Garcia, who is also an investigator in the Christopher S. Bond Life Sciences Center.
The finding was also surprising since another mouse model, which also mimicked CMT type 2e, did show nerve detachment. This other mouse model, developed by a team in Canada, had a mutation in the same gene but at a different site in the genetic code. According to Garcia, the lack of nerve detachment observed in his mouse model may point to different underlying mechanisms for CMT type 2e.
In a follow-up study, Garcia and colleagues showed that the mice they engineered also developed an abnormal gait. The scientists evaluated the gait of the mice using a so-called CatWalk system, a device that uses light and a high-speed camera to capture certain dynamics of a running mouse's footfalls. Abnormal gaiting was observed as a decreased paw print overlap and increased hind limb drag on the left side of the body, the authors report in the study.
A high-stepped gait is characteristic of people with CMT. Weakness of the foot and leg muscles often results in foot drop, an inability to move the ankle and toes properly, which is compensated for by raising the foot higher.
"It's an exciting time for CMT type2e," said Garcia. "With two really good mouse models, we're now in a powerful position to begin to ask questions about how the disease initiates and how it progresses."
Findings from the studies are published in the July 1, 2011, issue of the journal Human Molecular Genetics and in the January 30, 2012, online issue of the journal Genes, Brain, and Behavior.
|Contact: Timothy Wall|
University of Missouri-Columbia