The trajectory of gait development in mice

Abstract

Gait irregularities are prevalent in neurodevelopmental diseases and disorders (NDDs). However, there is a paucity of information on gait phenotypes in the NDD experimental models. This is in part due to the lack of understanding of the normal developmental trajectory of gait maturation in the mouse. Using the DigiGait system, we have developed a quantitative, standardized, and reproducible assay of developmental gait metrics in commonly used mouse strains that can be added to the battery of mouse model phenotyping. With this assay, we characterized the trajectory of gait in the developing C57BL/6J and FVB/AntJ mouse lines. In both lines, maturation of mouse gait between P21 and P30 was best reflected by aspects of the stance phase of the stride. Additionally, in C57BL/6J mice, gait maturation was observed through how the paw is loaded and unloaded during the stance phase of a stride. In FVB/AntJ mice, gait maturity during this developmental window was best observed through the decreased variability in paw area on the belt during stance. Our results also underscore the importance of considering body length when interpreting gait metrics. Further, our results show that background strain needs to be considered when comparing gait across models. Overall, our results show that aspects of mouse gait development parallel a timeline of normal human gait development, such as the percent of stride that is stance phase and swing phase. This study may be used as a standard reference for developmental gait phenotyping of a variety of murine models, such as models of neurodevelopmental disease.