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
-
- Animals
- Humans
- Immunohistochemistry
- Muscle, Skeletal/metabolism
- Myosin Heavy Chains/genetics
- Myosin Heavy Chains/metabolism
- Oculomotor Muscles*/metabolism
- Protein Serine-Threonine Kinases*/genetics
- Rho Guanine Nucleotide Exchange Factors*/genetics
- Zebrafish*
- Zebrafish Proteins/genetics
- PubMed
- 38334702 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Kahsay, A., Dennhag, N., Liu, J.X., Nord, H., Rönnbäck, H., Thorell, A.E., von Hofsten, J., Pedrosa Domellöf, F. (2024) Obscurin Maintains Myofiber Identity in Extraocular Muscles. Investigative ophthalmology & visual science. 65:1919.
Abstract
Purpose 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.
Methods 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.
Results 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.
Conclusions 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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping