Dysferlin is a plasma membrane protein and is expressed early in human development
Dysferlin is a plasma membrane protein and is expressed early in human development
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DOI：
10.1093/hmg/8.5.855
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发表时间：
1999-05-01
影响因子：
3.5
通讯作者：
Bushby, KMD
中科院分区：
文献类型：
--
作者：
Anderson, LVB;Davison, K;Bushby, KMD
最近，已经鉴定了在患有肢带型肌营养不良2B（LGMD 2B）和患有Miyoshi肌病（MM）的患者中突变的单个基因DYSF。这是令人感兴趣的，因为这些疾病被认为是两种不同的临床病症，因为不同的肌肉群是初始靶点，Dysferlin（该基因的蛋白质产物）是与任何已知的哺乳动物蛋白质没有同源性的新分子。我们现在已经提出了一种单克隆抗体dysferlin和报告的表达，这种新的蛋白质：免疫标记的抗体（指定NCL-哈姆雷特）证明了一种多肽的类似于230 kDa的蛋白质印迹的骨骼肌，与本地化的肌纤维膜显微镜在光和电子显微镜水平。在LGMD 2B/MM基因突变的患者中观察到dysferlin标记的特异性丢失。此外，具有两种不同移码突变的患者表现出非常低水平的免疫反应性蛋白，其方式让人联想到许多杜氏患者中表达的肌营养不良蛋白。对人类胎儿组织的分析表明，dysferlin在所检查的发育的最早阶段，即卡内基阶段15或16（胚胎年龄5-6周）表达。因此，Dysferlin存在于肢体开始显示区域分化的时候，在这个关键时刻缺乏Dysferlin可能有助于以后发展的肌肉受累模式，肌营养不良症的发作主要影响近端或远端肌肉。
Recently, a single gene, DYSF, has been identified which is mutated in patients with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy (MM), This is of interest because these diseases have been considered as two distinct clinical conditions since different muscle groups are the initial targets, Dysferlin, the protein product of the gene, is a novel molecule without homology to any known mammalian protein. We have now raised a monoclonal antibody to dysferlin and report on the expression of this new protein: immunolabelling with the antibody (designated NCL-hamlet) demonstrated a polypeptide of similar to 230 kDa on western blots of skeletal muscle, with localization to the muscle fibre membrane by microscopy at both the light and electron microscopic level. A specific loss of dysferlin labelling was observed in patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two different frameshifting mutations demonstrated very low levels of immunoreactive protein in a manner reminiscent of the dystrophin expressed in many Duchenne patients. Analysis of human fetal tissue showed that dysferlin was expressed at the earliest stages of development examined, at Carnegie stage 15 or 16 (embryonic age 5-6 weeks). Dysferlin is present, therefore, at a time when the limbs start to show regional differentiation, Lack of dysferlin at this critical time may contribute to the pattern of muscle involvement that develops later, with the onset of a muscular dystrophy primarily affecting proximal or distal muscles.