Differentiation of original and regenerated skeletal muscle fibres in mdx dystrophic muscles

Abstract

The differentiation of both original muscle fibres and the regenerated muscle fibres following necrosis in mdx muscles was investigated using immunoblotting and immunocytochemical procedures. Before the onset of necrosis, postnatal skeletal muscles in mdx mouse differentiated well with only a slight delay in differentiation indicated by the level of developmental isoforms of troponin T. Prior to the onset of apparent myopathic change, both fast and slow skeletal muscle fibre types in mdx leg muscles also differentiated well when investigated by analysis of specific myosin heavy chain expression pattern. While the original muscle fibres in mdx leg muscles developed well, the differentiation of regenerated myotubes into both slow and distinct fast muscle fibre types, however, was markedly delayed or inhibited as indicated by several clusters of homogeneously staining fibres even at 14 weeks of age. The number of slow myosin heavy chain-positive myotubes amongst the regenerated muscle clusters was quite small even in soleus. This study thus established that while muscle fibres initially develop normally with only a slight delay in the differentiation process, the differentiation of regenerated myotubes in mdx muscles is markedly compromised and consequently delayed.

Effect of cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca‐ATPase, on skeletal muscles from normal and mdx mice

“…On the basis of the developmental regulation of protein expression, these findings could also reflect slower muscular development in dystrophic EDL, leading to the persistent expression of the neonatal SERCA2a, which disappeared progressively during post-natal development. A recent study has also demonstrated a slight delay in the differentiation process of mdx muscles, indicated by the relative level of developmental isoforms of troponin T (Earnshaw et al 2002). In spite of the expression of the slow isoform of the SR Ca 2+ -pump in dystrophic EDL, our results do not indicate any shift in myosin expression to a slower isoform.…”

Disease course inmdx:utrophin+/−mice: comparison of three mouse models of Duchenne muscular dystrophy

“…), while other studies show a reverse trend (soleus: Earnshaw et al. ; vastus lateralis: Webster et al. ).…”

Efeito do ácido eicosapentaenoico na necrose e inflamação dos músculos distróficos de camundongos mdx

“…A fibra muscular em regeneração apresenta núcleo central com aspecto vesicular, citoplasma geralmente basófilo, refletindo alta síntese proteica e escassez de elementos contráteis, visível pelo número reduzido de estriações (Torres e Duchen, 1987). Já a fibra muscular completamente regenerada é caracterizada pela centro-nucleação, citoplasma eosinófilo e aumento da relação citoplasma/núcleo (Pastoret e Sebille, 1995;Earnshaw et al, 2002).…”