Abstract
Duchenne muscular dystrophy is an inherited degenerative muscle disease with progressive
weakness of skeletal and cardiac muscle. Disturbed calcium homeostasis and signalling
pathways result in degeneration/regeneration cycles with fibrotic remodelling of muscle
tissue, sustained by chronic inflammation. In addition to altered microarchitecture,
regeneration in dystrophic muscle fibres is often only classified by centrally located
nuclei but correlation of the regeneration process to nuclear volumes, myosin amounts,
architecture and functional quality are missing, in particular in old muscles where
the regenerative capacity is exhausted. Such information could yield novel regeneration-to-function
biomarkers. Here we used second harmonic generation and multi photon fluorescence
microscopy in intact single muscle fibres from wild-type, dystrophic mdx and transgenic
mdx mice expressing an Δex 17–48 mini-dystrophin to determine the percentage of centronucleated
fibres and nucleus-to-myosin volume ratio as a function of age. Based on this ratio
we define a ‘biomotoric efficiency’ as an optical measure for fibre maturation, which
is close to unity in adult wild-type and mini-dystrophin fibres, but smaller in very
young and old mdx mice as a result of ongoing cell maturation (young) and regeneration
(aged). With these parameters it is possible to provide a quantitative measure about
muscle fibre regeneration.
Keywords
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Article info
Publication history
Published online: May 02, 2014
Accepted:
April 23,
2014
Received:
February 21,
2014
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
