Gne depletion during zebrafish development impairs skeletal muscle structure and function

被引:15
|
作者
Daya, Alon [1 ,2 ]
Vatine, Gad David [3 ]
Becker-Cohen, Michal [1 ]
Tal-Goldberg, Tzukit [1 ]
Friedmann, Adam [2 ]
Gothilf, Yoav [3 ,4 ]
Du, Shao Jun [5 ]
Mitrani-Rosenbaum, Stella [1 ]
机构
[1] Hadassah Hebrew Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, IL-91240 Jerusalem, Israel
[2] Ruppin Acad Ctr, Sch Marine Sci, IL-40297 Michmoret, Israel
[3] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel
[4] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel
[5] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Inst Marine & Environm Technol, Baltimore, MD 21201 USA
基金
以色列科学基金会;
关键词
ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; BODY MYOPATHY MYOBLASTS; DISTAL MYOPATHY; RIMMED VACUOLES; BIFUNCTIONAL ENZYME; ACID BIOSYNTHESIS; POLYSIALIC ACID; SIALIC ACIDS; SIALYLATION; GENE;
D O I
10.1093/hmg/ddu045
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
GNE Myopathy is a rare recessively inherited neuromuscular disorder caused by mutations in the GNE gene, which codes for the key enzyme in the metabolic pathway of sialic acid synthesis. The process by which GNE mutations lead to myopathy is not well understood. By in situ hybridization and gne promoter-driven fluorescent transgenic fish generation, we have characterized the spatiotemporal expression pattern of the zebrafish gne gene and have shown that it is highly conserved compared with the human ortholog. We also show the deposition of maternal gne mRNA and maternal GNE protein at the earliest embryonic stage, emphasizing the critical role of gne in embryonic development. Injection of morpholino (MO)-modified antisense oligonucleotides specifically designed to knockdown gne, into one-cell embryos lead to a variety of phenotypic severity. Characterization of the gne knockdown morphants showed a significantly reduced locomotor activity as well as distorted muscle integrity, including a reduction in the number of muscle myofibers, even in mild or intermediate phenotype morphants. These findings were further confirmed by electron microscopy studies, where large gaps between sarcolemmas were visualized, although normal sarcomeric structures were maintained. These results demonstrate a critical novel role for gne in embryonic development and particularly in myofiber development, muscle integrity and activity.
引用
收藏
页码:3349 / 3361
页数:13
相关论文
共 50 条
  • [21] Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions
    Liu, Wenxuan
    Wei-LaPierre, Lan
    Klose, Alanna
    Dirksen, Robert T.
    Chakkalakal, Joe V.
    ELIFE, 2015, 4
  • [22] MUTATIONS AFFECTING SKELETAL-MUSCLE MYOFIBRIL STRUCTURE IN THE ZEBRAFISH
    FELSENFELD, AL
    WALKER, C
    WESTERFIELD, M
    KIMMEL, C
    STREISINGER, G
    DEVELOPMENT, 1990, 108 (03): : 443 - 459
  • [23] NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration
    Felipe Cabezas
    Claudio Cabello-Verrugio
    Natalia González
    Jeremy Salas
    Manuel J. Ramírez
    Eduardo de la Vega
    Hugo C. Olguín
    Biological Research, 56
  • [24] NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration
    Cabezas, Felipe
    Cabello-Verrugio, Claudio
    Gonzalez, Natalia
    Salas, Jeremy
    Ramirez, Manuel J.
    de la Vega, Eduardo
    Olguin, Hugo C.
    BIOLOGICAL RESEARCH, 2023, 56 (01)
  • [25] Hypoxia Impairs Muscle Function and Reduces Myotube Size in Tissue Engineered Skeletal Muscle
    Martin, Neil R. W.
    Aguilar-Agon, Kathyrn
    Robinson, George P.
    Player, Darren J.
    Turner, Mark C.
    Myers, Stephen D.
    Lewis, Mark P.
    JOURNAL OF CELLULAR BIOCHEMISTRY, 2017, 118 (09) : 2599 - 2605
  • [26] Myosin Quality Control Systems in Zebrafish Skeletal Muscle Development
    Carlisle, Casey
    Prill, Kendal
    Pilgrim, David
    FASEB JOURNAL, 2019, 33
  • [27] Inhibition of MAT2A Impairs Skeletal Muscle Repair Function
    Xiao, Wanli
    Huang, Tian-E
    Zhou, Jing
    Wang, Benhui
    Wang, Xiang
    Zeng, Weirong
    Wang, Qiquan
    Lan, Xinqiang
    Xiang, Yang
    BIOMOLECULES, 2024, 14 (09)
  • [28] Cholesterol depletion affects dihydropyridine receptor function in skeletal muscle cells
    Strube, C
    Carbonneau, L
    Blaineau, S
    Coronado, R
    Berthier, C
    BIOPHYSICAL JOURNAL, 2002, 82 (01) : 79A - 79A
  • [29] STRUCTURE AND FUNCTION OF THE SKELETAL MUSCLE EXTRACELLULAR MATRIX
    Gillies, Allison R.
    Lieber, Richard L.
    MUSCLE & NERVE, 2011, 44 (03) : 318 - 331
  • [30] Skeletal Muscle: A Brief Review of Structure and Function
    Walter R. Frontera
    Julien Ochala
    Calcified Tissue International, 2015, 96 : 183 - 195