Sawchak J A, Benoff B, Sher J H, Shafiq S A
Department of Neurology, State University of New York, Brooklyn 11203.
J Neurol Sci. 1990 Feb;95(2):183-92. doi: 10.1016/0022-510x(90)90241-e.
It has been suggested, on the basis of mostly morphological and some biochemical evidence, that defective innervation of muscle of patients with Werdnig-Hoffmann (WH) disease results in maturational arrest of the fibers at a stage comparable to 20-week gestational muscle. Therefore, with the use of recently developed and characterized, myosin-isoform-specific monoclonal antibodies (McAbs), an immunocytochemical study of muscle of 6 children with Werdnig-Hoffmann disease was done to determine if the pattern of expression of myosin heavy chain isoforms (MHC) in these fibers was similar to that of 20-week gestation muscle. This work showed that the MHC isoform expression in the muscle of the children with WH did not mimic that seen in 20-week gestation muscle since only a few fibers (less than 1-11%) in each specimen expressed prenatal MHC as detected by reactivity to McAb, ALD 180 (specific for a prenatal MHC) whereas virtually all of the fibers from 20-week gestation muscle were strongly reactive with ALD 180. The majority of the fibers expressed either adult fast MHC or adult slow MHC similar to that seen in normal muscle, although some co-expressed multiple MHC isoforms. Our results indicate that the difference of adult MHC isoforms in the muscle fibers of WH patients either proceeds in the absence of innervation or that denervation of muscle fibers is subsequent to the neural input required to initiate myosin isoform transitions to the adult isoforms.
基于大多是形态学和一些生物化学证据，有人提出，韦尔尼克 - 霍夫曼（WH）病患者的肌肉神经支配缺陷导致纤维成熟停滞在与妊娠20周肌肉相当的阶段。因此，利用最近开发和鉴定的肌球蛋白同工型特异性单克隆抗体（McAbs），对6例韦尔尼克 - 霍夫曼病患儿的肌肉进行了免疫细胞化学研究，以确定这些纤维中肌球蛋白重链同工型（MHC）的表达模式是否与妊娠20周肌肉的相似。这项研究表明，WH病患儿肌肉中的MHC同工型表达并不模仿妊娠20周肌肉中的情况，因为通过与McAb ALD 180（对产前MHC特异）反应检测到，每个标本中只有少数纤维（少于1 - 11%）表达产前MHC，而妊娠20周肌肉中的几乎所有纤维都与ALD 180强烈反应。大多数纤维表达成人快肌MHC或成人慢肌MHC，类似于正常肌肉中的情况，尽管有些纤维共表达多种MHC同工型。我们的结果表明，WH病患者肌肉纤维中成人MHC同工型的差异要么在没有神经支配的情况下发生，要么肌肉纤维的去神经支配是在启动肌球蛋白同工型向成人同工型转变所需的神经输入之后发生的。
