van der Ven P F, Jap P H, ter Laak H J, Nonaka I, Barth P G, Sengers R C, Stadhouders A M, Ramaekers F C
Department of Cell Biology and Histology, University of Nijmegen, The Netherlands.
J Neurol Sci. 1995 Apr;129(2):199-213. doi: 10.1016/0022-510x(94)00282-s.
We have studied the expression and distribution patterns of the intermediate filament proteins desmin and vimentin, the sarcomere components titin, nebulin and myosin, the basement membrane constituents collagen type IV and laminin, and the reticular layer component collagen type VI in skeletal muscle of patients with "classic" congenital myopathies (CM), using indirect immunofluorescence assays. In all biopsy specimens obtained from patients with central core disease (CCD), nemaline myopathy (NM), X-linked myotubular myopathy (XLMTM) and centronuclear myopathy (CNM), disease-specific desmin disturbances were observed. Vimentin was present in immature fibres in severe neonatal NM, and as sarcoplasmic aggregates in one case of CNM, while the amounts of vimentin and embryonic myosin, observed in XLMTM, decreased with age of the patients. Abnormal expression of myosin isoforms was found in several CM biopsies, although the organization of myosin and other sarcomere components was rarely disturbed. Basement membrane and reticular layer proteins were often prominently increased in severe cases of CM. We conclude that (i) desmin is a marker for individual types of CM and might be used for diagnostic purposes; (ii) the expression patterns of the differentiation markers desmin, vimentin and embryonic myosin in XLMTM, point either to a postnatal muscle fibre maturation or to a variable time-point of maturational arrest in individual patients; (iii) the correlation between the distribution patterns of extracellular matrix proteins and clinical presentation points to a role of these proteins in pathophysiology of CM.
我们运用间接免疫荧光分析法，研究了“经典”先天性肌病（CM）患者骨骼肌中中间丝蛋白结蛋白和波形蛋白、肌节成分肌联蛋白、伴肌动蛋白和肌球蛋白、基底膜成分IV型胶原蛋白和层粘连蛋白，以及网状层成分VI型胶原蛋白的表达和分布模式。在从患有中央核肌病（CCD）、杆状体肌病（NM）、X连锁肌管性肌病（XLMTM）和中心核性肌病（CNM）的患者获取的所有活检标本中，均观察到了疾病特异性的结蛋白紊乱。波形蛋白存在于严重新生儿期NM的未成熟纤维中，在1例CNM中以肌浆聚集体形式存在，而在XLMTM中观察到的波形蛋白和胚胎型肌球蛋白的量随患者年龄增长而减少。在一些CM活检标本中发现了肌球蛋白异构体的异常表达，尽管肌球蛋白和其他肌节成分的组织很少受到干扰。在严重的CM病例中，基底膜和网状层蛋白通常显著增加。我们得出以下结论：（i）结蛋白是个别类型CM的标志物，可用于诊断目的；（ii）XLMTM中结蛋白、波形蛋白和胚胎型肌球蛋白等分化标志物的表达模式，要么表明出生后肌纤维成熟，要么表明个别患者成熟停滞的时间点不同；（iii）细胞外基质蛋白的分布模式与临床表现之间的相关性表明这些蛋白在CM的病理生理学中起作用。
