Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants
Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants
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smyd1a 和 smyd1b 斑马鱼突变体中肌节组装缺陷
DOI：
10.1096/fj.201801578r
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发表时间：
2019-05-01
期刊：
影响因子：
4.8
通讯作者：
Du, Shaojun
中科院分区：
文献类型：
--
作者：
Cai, Mengxin;Han, Lichen;Du, Shaojun
已在斑马鱼中鉴定出两个smyd1类似物，smyd1a和smyd1b。虽然Smyd1b在快肌中的功能已经被报道，但它在慢肌中的功能以及Smyd1a的功能总体上是不确定的。在本研究中，我们产生了2个smyd1a突变等位基因，并分析了斑马鱼smyd1a和smyd1b单突变和双突变的肌肉缺陷。我们证明，单独敲除smyd1a对肌肉发育和鱼类生存没有明显影响。这与smyd1b突变体形成对比，smyd1b突变体表现出骨骼和心肌缺陷，导致早期胚胎死亡。然而，与单独的smyd1a或smyd1b突变相比，smyd1a和smyd1b双突变体表现出更强的肌肉缺陷，即在慢速和快速肌中肌节组织完全破坏。免疫染色显示，smyd1a；smyd1b双突变对斑马鱼胚胎肌球蛋白基因的表达没有影响，但导致斑马鱼胚胎肌肉细胞肌球蛋白蛋白水平的显著降低。伴随着HSP40和HSP90-1基因表达的上调。总之，我们的研究表明，Smyd1a和Smyd1b都参与了肌肉的缓慢和快速发育，尽管与Smyd1a相比，Smyd1b起着主导作用。Cai，M.，han，L.，Liu，L.，He，F.，Chu，W.，Zhang，J.，Tian，Z.，Du，S.斑马鱼突变体中肌节组装缺陷。
Two smyd1 paralogues, smyd1a and smyd1b, have been identified in zebrafish. Although Smyd1b function has been reported in fast muscle, its function in slow muscle and the function of Smyd1a, in general, are uncertain. In this study, we generated 2 smyd1a mutant alleles and analyzed the muscle defects in smyd1a and smyd1b single and double mutants in zebrafish. We demonstrated that knockout of smyd1a alone had no visible effect on muscle development and fish survival. This was in contrast to the smyd1b mutant, which exhibited skeletal and cardiac muscle defects, leading to early embryonic lethality. The smyd1a and smyd1b double mutants, however, showed a stronger muscle defect compared with smyd1a or smyd1b mutation alone, namely, the complete disruption of sarcomere organization in slow and fast muscles. Immunostaining revealed that smyd1a; smyd1b double mutations had no effect on myosin gene expression but resulted in a dramatic reduction of myosin protein levels in muscle cells of zebrafish embryos. This was accompanied by the up-regulation of hsp40 and hsp90-1 gene expression. Together, our studies indicate that both Smyd1a and Smyd1b partake in slow and fast muscle development although Smyd1b plays a dominant role compared with Smyd1a.Cai, M., Han, L., Liu, L., He, F., Chu, W., Zhang, J., Tian, Z., Du, S. Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants.