Vol. 94, Issue 5, 1744-1750, May 2003
Severe muscle dysfunction precedes collagen tissue
proliferation in mdx mouse diaphragm
Catherine
Coirault1,
Bernadette
Pignol2,
Racquel N.
Cooper3,
Gillian
Butler-Browne3,
Pierre-Etienne
Chabrier2, and
Yves
Lecarpentier1,4
1 Institut National de la Santé et de la
Recherche Médicale, Laboratoire d'Optique Appliquée, Ecole
Nationale Supérieure de Techniques Avancées, Ecole
Polytechnique, 91761 Palaiseau; 2 Institut Henri
Beaufour, 91966 Les Ulis; 3 Unité
Mixte de Recherche, Centre National de la Recherche Scientifique 7000,
75634 Paris; and 4 Service
d'Explorations Cardio-Respiratoires, Hôpital de Bicêtre,
Assistance Publique-Hôpitaux de Paris, 94275 Le
Kremlin-Bicêtre, France
After extensive necrosis, progressive
diaphragm muscle weakness in the mdx mouse is thought to
reflect progressive replacement of contractile tissue by
fibrosis. However, little has been documented on diaphragm
muscle performance at the stage at which necrosis and fibrosis are
limited. Diaphragm morphometric characteristics, muscle performance,
and cross-bridge (CB) properties were investigated in 6-wk-old control
(C) and mdx mice. Compared with C, maximum tetanic tension
and shortening velocity were 37 and 32% lower, respectively, in
mdx mice (each P < 0.05). The total number
of active CB per millimeter squared (13.0 ± 1.2 vs. 18.4 ± 1.7 × 109/mm2, P < 0.05)
and the CB elementary force (8.0 ± 0.2 vs. 9.0 ± 0.1 pN,
P < 0.01) were lower in mdx than in C. The
time cycle duration was lower in mdx than in C (127 ± 18 vs. 267 ± 61 ms, P < 0.05). Percentages of
fiber necrosis represented 2.8 ± 0.6% of the total muscle
fibers, and collagen surface area occupied 3.6 ± 0.7% in mdx diaphragm. Our results pointed to severe muscular
dysfunction in mdx mouse diaphragm, despite limited necrotic
and fibrotic lesions.
myosin; cross bridge; skeletal muscle; myopathy; muscular dystrophy
