Duchenne muscular dystrophy
(DMD) is the most prevalent fatal genetic disease of children and one of the most
common neuromuscular disorders. DMD is diagnosed as progressive muscle degeneration due to mutations in the
dystrophin gene resulting in loss of the dystrophin protein. Dystrophin while present
in skeletal and cardiac muscle, is also expressed in the smooth muscle and
endothelial cells of blood vessels1. Dystrophin provides structural
stability to the sarcolemmal membrane especially important under contractile
stress. It also localizes neuronal nitric oxide synthase to
the sarcolemma, which regulates vasorelaxation via nitric oxide release.
Therefore, dystrophin absence has been
implicated in vascular defects and ischemia in DMD2. These defects have not been fully explored
and their contribution to the pathology is ill-defined.
For this reason we chose to
characterize the dorsal skin panniculus carnosus (PC) skeletal muscle in the mdx
mouse model of DMD. The PC muscle was
chosen due to the high visibility of the microcirculation and relatively high
regenerative activity3 . The PC in mdx is a poorly documented
skeletal muscle. Therefore, to assess that PC exemplifies the dystrophic
phenotype, we applied two morphological indexes to transverse sections from
both mdx and wild-type (wt) mice; heterogeneity of myofiber
cross-sectional-area (CSA) and the percentage of central nucleated fibres
Herein, we found that PC muscle
from 5 week and 11 week old male mdx and wt mice showed high muscle
regeneration. PC in mdx demonstrated a higher percentage of CNF by 4-fold at
5-weeks and by 5-fold at 11-weeks of age compared to wt. The mean distribution
data of CSA revealed a significant shift towards increased fibre area in mdx at
both time points. Two
dimensional analyses of capillaries in PC muscles were performed at from 5 week
old mice revealed that the capillary
number/area was similar between mdx and wt.
However, capillary-to-fibre ratio was higher in mdx compared to wt
muscles at this 5 week time point.
In conclusion, the PC muscle shows
a high regenerative activity and exemplifies the DMD dystrophic phenotype.
Therefore, future studies on PC muscle in mdx mice will allow us to gain a
better insight into the vascular defects of DMD, and the testing of therapeutic
agents in ameliorating the disease using established techniques such as the
dorsal skinfold chamber model.