Abnormal localization of laminin subunits in muscular dystrophies.
To address potential involvement of muscle basal lamina and membrane cytoskeleton proteins in the etiology of non-dystrophinopathy muscular dystrophies, we examined the immunostaining intensity and distribution of laminin subunits (A, B1, B2 and M), type IV collagen, dystrophin and spectrin in skeletal muscle biopsies from 64 myopathic patients (17 Fukuyama congenital muscular dystrophy: FCMD, 13 congenital muscular dystrophy unrelated to FCMD: other CMD, 16 Duchenne muscular dystrophy: DMD, and 18 other neuromuscular diseases. In FCMD muscle, we found a significant reduction of laminin M (merosin; a striated muscle specific basal lamina-associated protein) with approximately 26% of levels seen in controls by quantitative immunofluorescence. Other CMD and DMD muscles showed less dramatic reductions (78%, 80%, respectively). The localization of laminin M was also abnormal in FCMD muscle. Laminin B1 and B2 showed abnormalities similar to those observed with laminin M, but were less marked. Laminin A was only detected in rare regenerating fibers in control biopsies, whereas it was seen around most muscle fibers in FCMD patients, and in dystrophin deficient muscle fibers from DMD patients and its carrier. Staining intensity of type IV collagen in FCMD muscle was not significantly different from the other diseases. These findings may implicate a primary or central role for the basal lamina in FCMD muscle.
Hayashi
Y K
YK
National Institute of Neuroscience, NCNP, Tokyo, Japan.
Engvall
E
E
Arikawa-Hirasawa
E
E
Goto
K
K
Koga
R
R
Nonaka
I
I
Sugita
H
H
Arahata
K
K
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D015153:Blotting, Western; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000276:immunology / Q000378:metabolism; D003720:Densitometry; D016189:Dystrophin / Q000276:immunology / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D013049:Spectrin / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016189:Dystrophin; D007074:Immunoglobulin G; D007797:Laminin; D013049:Spectrin; D003094:Collagen; D016650:Fluorescein-5-isothiocyanate