Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo
Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo
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DOI：
10.1016/j.yexcr.2006.10.005
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发表时间：
2007-01-01
影响因子：
3.7
通讯作者：
Lescure, Alain
中科院分区：
文献类型：
--
作者：
Deniziak, Marzanna;Thisse, Christine;Lescure, Alain
硒蛋白N（SelN）是一种功能未知的含硒蛋白，其基因编码突变可导致人类不同形式的先天性肌营养不良症。这些肌肉疾病的特征在于主要影响中轴肌的肌张力减退的早期发作。我们使用斑马鱼作为模型系统，以了解胚胎发育过程中的肌肉形成SelN的功能。斑马鱼SelN与其人类对应物高度同源，并且与人类肌肉疾病中的突变位置对应的氨基酸在斑马鱼蛋白中是保守的。Sepn1基因在发育早期的体节和脊索中高度表达。通过注射反义morpholinos抑制sepn1基因不会改变肌肉组织的命运，但会导致肌肉结构紊乱和运动性大大降低。肌节的超微结构分析揭示了肌肉肌节组织和肌纤维附着的缺陷，以及肌间隔完整性的改变。这些研究表明SelN在早期发育过程中对肌肉组织的重要作用。此外，肌原纤维结构和肌腱样结构的改变在胚胎缺乏SelN功能提供了新的见解SelN相关肌病的病理机制。(c)2006年爱思唯尔公司All rights reserved.
Mutations in the gene coding for selenoprotein N (SelN), a selenium containing protein of unknown function, cause different forms of congenital muscular dystrophy in humans. These muscular diseases are characterized by early onset of hypotonia which predominantly affect in axial muscles. We used zebrafish as a model system to understand the function of SelN in muscle formation during embryogenesis. Zebrafish SelN is highly homologous to its human counterpart and amino acids corresponding to the mutated positions in human muscle diseases are conserved in the zebrafish protein. The sepn1 gene is highly expressed in the somites and notochord during early development. Inhibition of the sepn1 gene by injection of antisense morpholinos does not alter the fate of the muscular tissue, but causes muscle architecture disorganization and greatly reduced motility. Ultrastructural analysis of the myotomes reveals defects in muscle sarcomeric organization and in myofibers attachment, as well as altered myoseptum integrity. These studies demonstrate the important role of SelN for muscle organization during early development. Moreover, alteration of myofibrils architecture and tendon-like structure in embryo deficient for SelN function provide new insights into the pathological mechanism of SelN-related myopathy. (c) 2006 Elsevier Inc. All rights reserved.