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Changes in muscle plasma membranes in young mice with X chromosome-linked muscular dystrophy: a freeze-fracture study
1Department of Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Abstract:
The structure of the muscle plasma membrane of tibialis anterior muscles of X chromosome-linked muscular dystrophy (mdx) mice was studied by the freeze-fracture technique at 3, 7 and 14 days after birth. The ultrastructural features of the freeze-fracture replicas of the muscle plasma membrane alterations in young mdx mice showed a decrease of orthogonal array, orthogonal array subunit particle and intramembranous particle densities on the protoplasmic face. The results are consistent with the previous studies which have shown that the orthogonal arrays are significantly decreased in number in muscle plasma membranes of adult mdx mice and in those of Duchenne dystrophy. However, the immature mdx mouse membranes at 3 days after birth contained as many orthogonal arrays as controls and did not show a statistically significant decrease (P greater than 0.1 by the Wilcoxon rank-sum test). Moreover, the orthogonal arrays were also numerous in young mdx mouse muscle plasma membranes at 7 and 14 days after birth, although the density was less than that of the control mice (P less than 0.01 by the Wilcoxon rank-sum test). These changes in young mdx mouse plasma membranes may precede the later muscle fibre degeneration in this mouse dystrophy and may provide us with an additional clue to the mechanism why mdx mice scarcely show any disability despite the absence of dystrophyn.
Insights
Early changes in muscle plasma membranes of young mdx mice, specifically reduced orthogonal array particle densities, may precede degeneration. These findings offer clues to the mild phenotype in X-linked muscular dystrophy mice despite dystrophin absence.
Area of Science:
- Muscle biology
- Cell membrane structure
- Muscular dystrophy research
Background:
- X chromosome-linked muscular dystrophy (mdx) mice are a model for Duchenne muscular dystrophy.
- Muscle plasma membrane alterations are implicated in muscular dystrophies.
- Orthogonal arrays in muscle membranes are crucial for structural integrity.
Purpose of the Study:
- To investigate early structural changes in the muscle plasma membrane of mdx mice.
- To analyze the density of orthogonal arrays and intramembranous particles in young mdx mice.
- To correlate early membrane alterations with the progression of muscular dystrophy.
Main Methods:
- Freeze-fracture electron microscopy was used to examine the tibialis anterior muscle plasma membrane.
- Analysis was performed at 3, 7, and 14 days after birth in mdx mice and controls.
- Quantification of orthogonal array, orthogonal array subunit particle, and intramembranous particle densities was conducted.
Main Results:
- A decrease in orthogonal array, orthogonal array subunit particle, and intramembranous particle densities was observed in young mdx mice.
- At 3 days postpartum, mdx mouse membranes showed no significant difference in orthogonal arrays compared to controls.
- By 7 and 14 days, mdx mouse membranes exhibited fewer orthogonal arrays than controls, though still numerous.
Conclusions:
- Early alterations in muscle plasma membrane structure, particularly reduced orthogonal array density, occur in young mdx mice.
- These changes may precede the onset of muscle fiber degeneration in mdx mice.
- The findings suggest a potential mechanism for the relatively mild phenotype observed in mdx mice despite dystrophin deficiency.