Researchers Detail Abnormalities in Gaits of Mice With Angelman

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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

“Gait analysis proved a reliable, translational assay that can accomplish within-subject lifespan development, regression, progression and/or decline without confounding test–retest effects,” its researchers wrote.

The study, “Gait as a quantitative translational outcome measure in Angelman syndrome,” was published in Autism Research.

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

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

Results showed that, compared with wild-type mice, mice with Angelman tended to keep their feet wider apart while walking, which likely indicates that the mice were having trouble keeping their balance.

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

Angelman mice also tended to take fewer, longer steps compared with their wild-type counterparts. The researchers noted that taking fewer, longer steps is generally associated with running (imaging a horse galloping, or a person sprinting). As the mice were going a fixed speed on a treadmill, this difference in gait may reflect the Angelman mice having to “run” to go the speed done for tests, while the wild-type mice were able to walk.

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

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

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