Unusual laminin alpha2 processing in myoblasts from a patient with a novel variant of congenital muscular dystrophy.
We recently described a novel congenital muscular dystrophy (CMD) syndrome characterized by mental retardation, microcephaly, and partial merosin deficiency on muscle biopsy. Linkage analysis excluded involvement of the known CMD loci. We now report on a study performed on the differentiation of cultured myoblasts from one patient affected by this condition to evaluate the potential to form myotubes and merosin processing in these cells. The differentiation rate was comparable to controls and myotubes were stable in culture. Biochemical analysis showed the expected 80-kDa merosin subunit in myoblasts. However, a shifted 60-kDa protein was detected in myotubes. Matrix-metalloproteinases (MMPs) zymography showed increased gelatinolytic activity, and immunoblotting identified an increased amount of membrane-type 1 matrix-metalloproteinase in pathological myotube preparations. Our results show that these CMD-derived myotubes contain a low molecular weight merosin. They further suggest that an altered regulation of MMPs can be involved in basal lamina damage.
Lattanzi
G
G
Institute of Normal and Pathological Cytomorphology, CNR, Bologna, Italy.
Muntoni
F
F
Sabatelli
P
P
Squarzoni
S
S
Maraldi
N M
NM
Cenni
V
V
Villanova
M
M
Columbaro
M
M
Merlini
L
L
Marmiroli
S
S
D002454:Cell Differentiation; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D009136:Muscular Dystrophies / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
D007797:Laminin; C102645:laminin alpha 2; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2