Development of muscle pathology in canine X-linked muscular dystrophy. II. Quantitative characterization of histopathological progression during postnatal skeletal muscle development.
We have characterized the time course of muscle pathology development during the postnatal maturation of quadriceps and tibialis anterior muscle in dystrophic golden retriever dogs. We determined the percentages of degenerating, regenerating, calcium-positive, hypercontracted, albumin-positive, and C3 complement fraction-positive muscle fibers and the extent of connective tissue proliferation in animals from neonate to adult. Necrotic fibers increased from days 2 to 30, decreased at 60 days (to 0.8%) and increased in older animals to a stable level of around 2%. Hypercontracted fibers peaked at 15 days (19.1%) and declined to 3.7% in adults. Regenerating fibers were numerous at 15 and 30 days (10%), declined at 60 days to 4.7% and declined further in adults. Calcium- and albumin-positive fibers peaked at 30 days (6.5% and 13.8%, respectively) and then declined to around 3% and 5%, respectively, in older dogs. In dystrophic dogs, the extent of fibrosis was significantly greater on 15 days than in controls, but did not then increase with age. In carriers, calcium- and albumin-positive fibers always expressed dystrophin abnormally. Muscle damage occurs before completion of muscle maturation in dystrophic dogs. While necrosis and hypercontraction remain stable in adults, fiber regeneration declines to very low levels. In contrast to Duchenne muscular dystrophy, muscle fibrosis in the muscle studied does not increase with age.
Cozzi
F
F
Department of Neuromuscular Diseases, Istituto Nazionale Neurologico C. Besta, Milano, Italy.
Cerletti
M
M
Luvoni
G C
GC
Lombardo
R
R
Brambilla
P G
PG
Faverzani
S
S
Blasevich
F
F
Cornelio
F
F
Pozza
O
O
Mora
M
M
D000375:Aging / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D007150:Immunohistochemistry; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology* / Q000503:physiopathology; D009336:Necrosis; D014960:X Chromosome / Q000235:genetics / Q000473:pathology*