Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.
M-laminin is a major member of the laminin family of basement membrane proteins. It is prominently expressed in striated muscle and peripheral nerve. M-laminin is deficient in patients with the autosomal recessive Fukuyama congenital muscular dystrophy but is normal in patients with the sex-linked Duchenne and Becker muscular dystrophies. We have examined M-laminin expression in mice with autosomal recessive muscular dystrophy caused by the mutation dy. The heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting in homozygous dystrophic dy/dy mice but was normal in heterozygous and wild-type nondystrophic mice. Immunofluorescence confirmed the presence of other major basement membrane proteins in the dystrophic mice. Very low levels of M-laminin heavy chain mRNA were detected by Northern blotting of muscle and heart tissue from dy/dy mice, suggesting that M-laminin heavy-chain mRNA may be produced at very low levels or is unstable. Information about the chromosomal localization of the M heavy-chain in human and mouse suggests that a mutation in the M-chain gene causes the muscular dystrophy in dy/dy mice. The dy mouse may provide a model for autosomal muscular dystrophies in humans and facilitate studies of functions of M-laminin.
Xu
H
H
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037.
Christmas
P
P
Wu
X R
XR
Wewer
U M
UM
Engvall
E
E
D000818:Animals; D001485:Basement Membrane / Q000473:pathology*; D015870:Gene Expression; D007797:Laminin / Q000172:deficiency*; D051379:Mice; D008817:Mice, Mutant Strains; D009132:Muscles / Q000648:ultrastructure*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics
D007797:Laminin; D012333:RNA, Messenger