Plantarflexion contracture in the mdx mouse

Abstract

Objective: Contractures are a major clinical issue for patients with muscular dystrophies. However, it is unknown whether contractures are present in the widely used mdx mouse model of Duchenne muscular dystrophy. Therefore, the objectives of this study were to develop methods to measure muscle contractures in mice, to determine whether plantarflexion contractures are present in mdx mice, and to analyze the composition of the major muscles involved.

Design: Hindlimbs of eight wild type and six mdx mice were assessed every 2 wks during the course of a 12-wk study. Assessments included range of motion and in vivo torques about the ankle. At the end of the study, mice were euthanized, and muscles were analyzed for composition.

Results: The mdx mice had ∼10 degrees less dorsiflexion, increased passive torque moving the ankle into dorsiflexion, and an increased passive-to-active torque ratio relative to wild type mice. Gastrocnemius muscle composition alterations included increased wet mass, decreased protein content, and increased collagen.

Conclusions: The results indicate that mdx mice have plantarflexion contractures similar to those seen in children with Duchenne muscular dystrophy. In future studies, these measures can be used to assess strategies to slow the progression of contractures that occur with muscular dystrophies.

FIGURE 1

Dorsiflexion excursion was measured in WT and mdx mice from 6 to 18 wks of age. Values represent means. Error bars represent SE. There was an interaction between mouse group and age (P = 0.013). *Different from WT at corresponding age; ^#different from wk 6 within group; ^$different from wk 8 within group.

FIGURE 2

Passive torque about the ankle was measured at 5-degree intervals from 20 degrees of plantarflexion to 20 degrees of dorsiflexion, with 0 degree defined as the foot being perpendicular to the tibia. Passive torque data shown are those that were measured at 6 wks of age in WT and mdx mice and are normalized to body weight. There was an interaction between mouse group and angle (P = 0.003). *Different from WT at corresponding angle.

FIGURE 3

Ratio of passive torque of the plantarflexors to the active torque of the dorsiflexors in WT and mdx mice from 6 to 18 wks of age. Values represent means. Error bars represent SE. *Main effect of mouse group (P = 0.029).

FIGURE 4

Relative contents of dry mass (A), total protein (B), and collagen (C) in tibialis anterior and gastrocnemius muscles of WT and mdx mice at the end of the study when mice were 19 wks of age. *Different from WT.