ZFIN ID: ZDB-PUB-180718-10
Knockout of myomaker results in defective myoblast fusion, reduced muscle growth and increased adipocyte infiltration in zebrafish skeletal muscle
Shi, J., Cai, M., Si, Y., Zhang, J., Du, S.
Date: 2018
Source: Human molecular genetics   27(20): 3542-3554 (Journal)
Registered Authors: Du, Shao Jun (Jim)
Keywords: none
MeSH Terms:
  • Adipocytes/physiology
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Gene Knockout Techniques
  • Larva/genetics
  • Larva/growth & development
  • Larva/metabolism
  • Larva/physiology
  • Membrane Proteins/genetics
  • Membrane Proteins/physiology*
  • Mobius Syndrome/metabolism
  • Mobius Syndrome/physiopathology*
  • Morphogenesis
  • Muscle Development*
  • Muscle Proteins/genetics
  • Muscle Proteins/physiology*
  • Muscle, Skeletal/growth & development
  • Muscle, Skeletal/metabolism
  • Muscle, Skeletal/physiopathology*
  • Muscular Diseases/metabolism
  • Muscular Diseases/physiopathology*
  • Myoblasts/metabolism*
  • Myoblasts/physiology
  • Pierre Robin Syndrome/metabolism
  • Pierre Robin Syndrome/physiopathology*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 30016436 Full text @ Hum. Mol. Genet.
The fusion of myoblasts into multinucleated muscle fibers is vital to skeletal muscle development, maintenance, and regeneration. Genetic mutations in the Myomaker (mymk) gene cause Carey-Fineman-Ziter syndrome in human populations. To study the regulation of myomaker gene expression and function, we generated three myomaker mutant alleles in zebrafish using CRISPR and analyzed the effects of myomaker knockout on muscle development and growth. Our studies demonstrated that knockout of myomaker resulted in defective myoblast fusion in zebrafish embryos and increased mortality at larval stage around 35-45 days post-fertilization. The viable homozygous mutants were smaller in size and weighed approximately 1/3 the weight of the wild type sibling at 3 months old. The homozygous mutants showed craniofacial deformities, resembling the facial defect observed in human populations with Carey-Fineman-Ziter syndrome. Histological analysis revealed that skeletal muscles of myomaker mutants contained mainly small size fibers and substantial intramuscular adipocyte infiltration. Single fiber analysis revealed that myofibers in myomaker mutant were predominantly single nucleated fibers. However, myofibers with multiple myonuclei were observed, although the number of nuclei per fiber was much less compared with that in WT fibers. Overexpression of sonic Hedgehog inhibited myomaker expression in zebrafish embryos and blocked myoblast fusion. Collectively, these studies demonstrated that Myomaker is essential for myoblast fusion during muscle development and growth.