PUBLICATION
Knockout of Shelterin subunit genes in zebrafish results in distinct outcomes
- Authors
- Ma, J., Tang, D., Gao, P., Liang, S., Zhang, R.
- ID
- ZDB-PUB-220607-27
- Date
- 2022
- Source
- Biochemical and Biophysical Research Communications 617: 22-29 (Journal)
- Registered Authors
- Zhang, Ruilin
- Keywords
- Shelterin complex, Telomere, Zebrafish disease model, acd
- MeSH Terms
-
- Animals
- Male
- Shelterin Complex
- Telomerase*/metabolism
- Telomere/genetics
- Telomere/metabolism
- Telomere-Binding Proteins/genetics
- Telomere-Binding Proteins/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 35667242 Full text @ Biochem. Biophys. Res. Commun.
Citation
Ma, J., Tang, D., Gao, P., Liang, S., Zhang, R. (2022) Knockout of Shelterin subunit genes in zebrafish results in distinct outcomes. Biochemical and Biophysical Research Communications. 617:22-29.
Abstract
As the core component of telomeres, the Shelterin complex interacts with telomerase and the CST complex and plays a crucial role in maintaining telomere structure. Perturbation of Shelterin subunits results in telomere damage and subsequent genomic instability, which leads to aging as well as multiple human diseases. Recently, zebrafish have been widely utilized to model human diseases. To establish appropriate zebrafish models of Shelterin-related human disorders, we generated knockout zebrafish of the Shelterin subunit genes acd, pot1, tinf2, terf1 and pinx1 using the CRISPR/Cas9 technology and analyzed the effects of gene deficiency on zebrafish development in detail. We discovered that tinf2, terf1 and pinx1 homozygous mutants could grow to adulthood normally, whereas acd and pot1 homozygous mutant larvae died between 12 and 15 dpf without obvious abnormalities. A few acd-/- mutants survived to adulthood and displayed several premature aging-like phenotypes, including male sterility, cachectic dwarfism and reduced lifespan. Overall, our study established a variety of telomere-deficient zebrafish mutant strains and provided novel animal models for further exploring the relationship between telomeres and aging as well as the pathogenesis of human diseases associated with telomere deficiency.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping