Researchers detail gait abnormalities in Angelman mice

Mice with Angelman syndrome (AS) show clear abnormalities in walking patterns, and assessing these patterns may be useful in measuring the effectiveness of potential therapies, a new study indicates.

“Gait analysis has been shown to be a reliable translational test that can accomplish a subject’s development, regression, progression, and/or decline in lifespan without confounding test-retest effects,” wrote writes its researchers.

The study, “Walking as a Quantitative Measure of Translational Outcomes in Angelman Syndromewas published in autism research.

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Almost all people with Angelman develop motor problems, which can include tremors, spasticity, and lack of coordination. These can cause walking difficulties or abnormalities. In this study, a team led by researchers from the University of California Davis School of Medicine performed detailed analyzes of walking patterns in Angelman model mice.

Gait analysis was performed using an automated test called DigiGait. Basically, the mice were asked to walk or run on a treadmill and recorded with a specially placed camera. The videos were then processed and analyzed via a computer to objectively assess differences in gait patterns over time and space.

The results showed that, compared to the wild-type mice, the mice with Angelman tended to keep their feet further apart while walking, likely indicating that the mice had trouble keeping their balance.

“We observed wider stances in both sets of limbs in juveniles and adults, an indicator of instability since the wider stances serve as a compensatory measure for imbalance during gait,” the researchers wrote.

Angelman mice also tended to take fewer and longer steps than their wild-type counterparts. The researchers noted that taking fewer and longer steps is usually associated with running (imagining a galloping horse or a sprinting person). Because the mice went at a fixed speed on a treadmill, this difference in gait may reflect the fact that the Angelman mice had to “run” to reach the indicated speed for the tests, while the wild-type mice were able to walk.

Analyzes of mice at different ages showed that gait differences between Angelman mice and wild-type mice were evident from the earliest times tested – around the time the mice were weaned, which was the first time that they could reliably walk on the treadmill for the test – and the differences remained clear throughout the mice’s lives.

Based on these findings, the researchers proposed that gait assessments might be a useful measure to assess potential treatments for Angelman. They noted that further research could identify specific mouse gait parameters that may be most relevant to effects in humans, noting that motor development in the two species is very similar.

“Walking is a versatile quantitative outcome measure with great potential for use in therapeutic assessment,” the team concluded.

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