Presence of laminin alpha5 chain and lack of laminin alpha1 chain during human muscle development and in muscular dystrophies.
There is currently a great interest in identifying laminin isoforms expressed in developing and regenerating skeletal muscle. Laminin alpha1 has been reported to localize to human fetal muscle and to be induced in muscular dystrophies based on immunohistochemistry with the monoclonal antibody 4C7, suggested to recognize the human laminin alpha1 chain. Nevertheless, there seems to be no expression of laminin alpha1 protein or mRNA in developing or dystrophic mouse skeletal muscle fibers. To address the discrepancy between the results obtained in developing and dystrophic human and mouse muscle we expressed the E3 domain of human laminin alpha1 chain as a recombinant protein and made antibodies specific for human laminin alpha1 chain (anti-hLN-alpha1G4/G5). We also made antibodies to the human laminin alpha5 chain purified from placenta. In the present report we show that hLN-alpha1G4/G5 antibodies react with a 400-kDa laminin alpha1 chain and that 4C7 reacts with a 380-kDa laminin alpha5 chain. Immunohistochemistry with the hLN-alpha1G4/G5 antibody and 4C7 revealed that the two antibodies stained human kidney, developing and dystrophic muscle in distinct patterns. Our data indicate that the previously reported expression patterns in developing, adult, and dystrophic human muscle tissues with 4C7 should be re-interpreted as an expression of laminin alpha5 chain. Our data are also consistent with earlier work in mouse, indicating that laminin alpha1 is largely an epithelial laminin chain not present in developing or dystrophic muscle fibers.
Tiger
C F
CF
Department of Animal Physiology, Uppsala University, BMC, Box 596, S-751 24 Uppsala, Sweden.
Champliaud
M F
MF
Pedrosa-Domellof
F
F
Thornell
L E
LE
Ekblom
P
P
Gullberg
D
D
D000328:Adult; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007668:Kidney / Q000737:chemistry; D007797:Laminin / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D024510:Muscle Development; D009132:Muscles / Q000196:embryology; D009136:Muscular Dystrophies / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007797:Laminin; D011994:Recombinant Proteins; C097043:laminin alpha5; C084098:laminin A