Developing a Mouse Model of Chronic Ankle Instability

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Abstract

Introduction

Ankle sprains are the most common orthopedic pathology experienced during sport and physical activity and often result in chronic ankle instability (CAI). Understanding how to prevent CAI is difficult because of the costs and logistics associated with clinical trials aimed at preventing the heterogeneous symptoms associated with CAI. Thus, a need exists to develop an animal model that presents similar long-term consequences as CAI to assess preclinical data. Thus, the purpose was to determine whether surgically transecting the lateral ligaments of a mouse hind limb results in the development of CAI-like symptoms 12 months after injury.

Methods

Thirty male mice (CBA/J) were randomly placed into a SHAM (control), CFL (calcaneofibular ligament; mild ankle sprain), or ATFL/CFL (anterior talofibular ligament/CFL; severe) ankle sprain group and housed individually. Three days after surgically transecting the respective lateral ligaments, mice were given a solid surface running wheel and daily running wheel measurements were recorded. Outcome measures of balance and gait were obtained before and at 4, 48, 54, and 60 wk after injury.

Results

The ATFL/CFL group had significantly more hind foot slips than the CFL and SHAM groups (P < 0.05). The CFL also had more hind foot slips relative to the SHAM group (P < 0.05). The ATFL/CFL group was significantly less physically active relative to the SHAM and CFL groups (P < 0.05). A cut score of 4.75 foot slips had a sensitivity of 0.68 and specificity of 1.00 and indicates that 70% (14/20) of mice with an ankle sprain had developed CAI.

Conclusions

The results of this study indicate that an acute ankle sprain in mice can result in the development of CAI-like symptoms 12 months after injury.

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