PUBLICATION

Obscurin Maintains Myofiber Identity in Extraocular Muscles

Authors
Kahsay, A., Dennhag, N., Liu, J.X., Nord, H., Rönnbäck, H., Thorell, A.E., von Hofsten, J., Pedrosa Domellöf, F.
ID
ZDB-PUB-240210-3
Date
2024
Source
Investigative ophthalmology & visual science   65: 1919 (Journal)
Registered Authors
Nord, Hanna, von Hofsten, Jonas
Keywords
none
MeSH Terms
  • Zebrafish Proteins/genetics
  • Muscle, Skeletal/metabolism
  • Rho Guanine Nucleotide Exchange Factors*/genetics
  • Humans
  • Animals
  • Oculomotor Muscles*/metabolism
  • Myosin Heavy Chains/genetics
  • Myosin Heavy Chains/metabolism
  • Protein Serine-Threonine Kinases*/genetics
  • Zebrafish*
  • Immunohistochemistry
(all 11)
PubMed
38334702 Full text @ Invest. Ophthalmol. Vis. Sci.
Abstract
The cytoskeleton of the extraocular muscles (EOMs) is significantly different from that of other muscles. We aimed to investigate the role of obscurin, a fundamental cytoskeletal protein, in the EOMs.
The distribution of obscurin in human and zebrafish EOMs was compared using immunohistochemistry. The two obscurin genes in zebrafish, obscna and obscnb, were knocked out using CRISPR/Cas9, and the EOMs were investigated using immunohistochemistry, qPCR, and in situ hybridization. The optokinetic reflex (OKR) in five-day-old larvae and adult obscna-/-;obscnb-/- and sibling control zebrafish was analyzed. Swimming distance was recorded at the same age.
The obscurin distribution pattern was similar in human and zebrafish EOMs. The proportion of slow and fast myofibers was reduced in obscna-/-;obscnb-/- zebrafish EOMs but not in trunk muscle, whereas the number of myofibers containing cardiac myosin myh7 was significantly increased in EOMs of obscurin double mutants. Loss of obscurin resulted in less OKRs in zebrafish larvae but not in adult zebrafish.
Obscurin expression is conserved in normal human and zebrafish EOMs. Loss of obscurin induces a myofiber type shift in the EOMs, with upregulation of cardiac myosin heavy chain, myh7, showing an adaptation strategy in EOMs. Our model will facilitate further studies in conditions related to obscurin.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
umu16
    Indel
    umu23
      Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      obscnaCRISPR1-obscnaCRISPR
      obscnbCRISPR1-obscnbCRISPR
      1 - 2 of 2
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      Fish
      No data available
      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      No data available
      Mapping