Xu H, Christmas P, Wu X R, Wewer U M, Engvall E
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037.
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5572-6. doi: 10.1073/pnas.91.12.5572.
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.
M-层粘连蛋白是基底膜蛋白层粘连蛋白家族的主要成员。它在横纹肌和周围神经中显著表达。患有常染色体隐性遗传的福山型先天性肌营养不良的患者体内M-层粘连蛋白缺乏，但患有X连锁的杜氏和贝克型肌营养不良的患者体内M-层粘连蛋白正常。我们已经检测了由dy突变引起的常染色体隐性遗传性肌营养不良小鼠中M-层粘连蛋白的表达。通过免疫荧光和免疫印迹法，在纯合营养不良的dy/dy小鼠的骨骼肌、心肌和周围神经中未检测到M-层粘连蛋白的重链，但在杂合和野生型非营养不良小鼠中其重链正常。免疫荧光证实了营养不良小鼠中存在其他主要的基底膜蛋白。通过对dy/dy小鼠肌肉和心脏组织进行Northern印迹分析，检测到极低水平的M-层粘连蛋白重链mRNA，这表明M-层粘连蛋白重链mRNA可能以极低水平产生或不稳定。关于人类和小鼠中M重链染色体定位的信息表明，M链基因中的突变导致了dy/dy小鼠的肌营养不良。dy小鼠可能为人类常染色体性肌营养不良提供一个模型，并有助于对M-层粘连蛋白功能的研究。
