DEFECTIVE MUSCLE BASEMENT-MEMBRANE AND LACK OF M-LAMININ IN THE DYSTROPHIC DY/DY MOUSE
DEFECTIVE MUSCLE BASEMENT-MEMBRANE AND LACK OF M-LAMININ IN THE DYSTROPHIC DY/DY MOUSE
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DOI：
10.1073/pnas.91.12.5572
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
ENGVALL, E
中科院分区：
文献类型：
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作者：
XU, H;CHRISTMAS, P;ENGVALL, E
M-层粘连蛋白是基底膜蛋白层粘连蛋白家族的主要成员。在横纹肌和周围神经中有显著表达。层粘连蛋白在常染色体隐性遗传的福山先天性肌营养不良症患者中缺乏，但在性连锁的杜氏肌营养不良症和贝克尔肌营养不良症患者中正常。我们研究了由突变dy引起的常染色体隐性肌营养不良症小鼠的M-层粘连蛋白表达。免疫荧光和免疫印迹法在纯合子营养不良dy/dy小鼠的骨骼肌、心肌和外周神经中检测不到M-层粘连蛋白重链，但在杂合子和野生型非营养不良小鼠中检测到。免疫荧光证实了营养不良小鼠中其他主要基底膜蛋白的存在。通过dy/dy小鼠肌肉和心脏组织的北方印迹法检测到非常低水平的M-层粘连蛋白重链mRNA，表明M-层粘连蛋白重链mRNA可能以非常低的水平产生或不稳定。关于人和小鼠中M重链的染色体定位的信息表明，M链基因中的突变导致dy/dy小鼠的肌营养不良症。dy小鼠可为人类常染色体肌营养不良症提供模型，并有助于研究M-层粘连蛋白的功能。
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.