Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy.
OBJECTIVE
We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered.


METHODS
Unfixed biopsies of control and FSHD deltoid and biceps muscles, snap-frozen at resting length, were cryosectioned, indirectly immunolabeled with fluorescent antibodies to sarcolemmal and myofibrillar markers, and examined with confocal microscopy to localize the immunolabeled proteins. Glutaraldehyde-fixed samples were stained with heavy metals, embedded, thin-sectioned, and examined with electron microscopy to determine the relationship between the sarcolemma and the underlying myofibrils.


RESULTS
Confocal microscopy showed that some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underlying contractile apparatus. Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100 nm in controls to values as high as 550 nm in FSHD.


CONCLUSIONS
Our results show that the pathophysiology of FSHD includes novel changes in the organization of the sarcolemma and its association with nearby contractile structures and suggest that, as in other muscular dystrophies, the integrity of the sarcolemma may be compromised in FSHD.
Reed
Patrick
P
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Porter
Neil C
NC
Strong
John
J
Pumplin
David W
DW
Corse
Andrea M
AM
Luther
Paul W
PW
Flanigan
Kevin M
KM
Bloch
Robert J
RJ
D003599:Cytoskeleton / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000473:pathology* / Q000503:physiopathology*; D012508:Sarcolemma / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013049:Spectrin / Q000378:metabolism
D009124:Muscle Proteins; D013049:Spectrin