δ-Sarcoglycan is required for early zebrafish muscle organization
δ-Sarcoglycan is required for early zebrafish muscle organization
复制标题
DOI：
10.1016/j.yexcr.2004.10.032
复制
发表时间：
2005-03-10
影响因子：
3.7
通讯作者：
Kunkel, LM
中科院分区：
文献类型：
--
作者：
Guyon, JR;Mosley, AN;Kunkel, LM
肌聚糖（α -、β -、γ -和δ -）突变与人类肢带性肌营养不良（LGMD） 2C-F型有关。我们克隆了斑马鱼编码三角肌聚糖的同源基因，并将该基因定位到连锁群21。预测的斑马鱼三角肌聚糖蛋白与其人类同源物高度同源，包括三个预测糖基化位点中的两个。与肌营养不良蛋白相关蛋白复合体（DAPC）的其他成员一样，在成年斑马鱼中，三角肌聚糖定位于肌纤维的肌层膜，但在发育中的胚胎中，在肌间隔处更为明显。斑马鱼胚胎注射抗三角肌聚糖的morpholinos后，在5 dpf时相对不活跃，肌纤维紊乱，鱼鳔不膨胀。免疫组织化学和免疫印迹实验表明，δ、β和γ -肌聚糖在变形体中均下调，而肌营养不良蛋白的表达不受影响。虽然缺乏三角肌聚糖的人主要表现为成人表型，但我们的研究结果表明，三角肌聚糖在斑马鱼早期肌肉发育中起作用。(C) 2004爱思唯尔公司版权所有。
Mutations in sarcoglycans (alpha-, beta-, gamma-, and delta-) have been linked with limb girdle muscular dystrophy (LGMD) types 2C-F in humans. We have cloned the zebrafish orthologue encoding delta-sarcoglycan and mapped the gene to linkage group 21. The predicted zebrafish delta-sarcoglycan protein is highly homologous with its human orthologue including conservation of two of the three predicted glycosylation sites. Like other members of the dystrophin-associated protein complex (DAPC), delta-sarcoglycan localizes to the sarcolemmal membrane of the myofiber in adult zebrafish, but is more apparent at the myosepta in developing embryos. Zebrafish embryos injected with morpholinos against delta-sarcoglycan were relatively inactive at 5 dpf, their myofibers were disorganized, and swim bladders uninflated. Immunohistochemical and immunoblotting experiments show that delta-, beta-, and gamma-sarcoglycans were all downregulated in the morphants, whereas dystrophin expression was unaffected. Whereas humans lacking delta-sarcoglycan primarily show adult phenotypes, our results suggest that delta-sarcoglycan plays a role in early zebrafish muscle development. (C) 2004 Elsevier Inc. All rights reserved.