PUBLICATION
Zonular defects in loxl1-deficient zebrafish
- Authors
- Zhang, M., Sun, S., Wang, L., Wang, X., Chen, T., Chen, Z., Jiang, Y.
- ID
- ZDB-PUB-210930-3
- Date
- 2021
- Source
- Clinical & experimental ophthalmology 50(1): 62-73 (Journal)
- Registered Authors
- Wang, Xu
- Keywords
- Exfoliation Syndrome, LOXL1, Lens Subluxation, Zebrafish, Zonules
- MeSH Terms
-
- Amino Acid Oxidoreductases/genetics
- Amino Acid Oxidoreductases/metabolism
- Animals
- Exfoliation Syndrome*/genetics
- Polymorphism, Single Nucleotide
- Zebrafish*/metabolism
- PubMed
- 34585825 Full text @ Clin Exp Ophthalmol
Citation
Zhang, M., Sun, S., Wang, L., Wang, X., Chen, T., Chen, Z., Jiang, Y. (2021) Zonular defects in loxl1-deficient zebrafish. Clinical & experimental ophthalmology. 50(1):62-73.
Abstract
Background To investigate the roles of the lysyl oxidase-like 1 (loxl1) gene in zebrafish eye development and the potency of loxl1 deficiency in mimicking the ocular manifestations of Exfoliation Syndrome (XFS).
Methods CRISPR/Cas9 technology was used to generate a frameshift coding deletion in zebrafish loxl1. Expression profiles and ocular manifestations of the wildtype, heterozygous mutant (loxl1+/- ) and homozygous mutant (loxl1-/- ) zebrafish were analyzed in a range of developmental stages from zebrafish larvae to dissected adult zebrafish eyes.
Results The loxl1 deficiency caused zonular bundling disorders in juvenile zebrafish and accumulation of pearl-like particles adhering to the adult zebrafish zonule. The bundles appeared to lack form and were thinner in both loxl1+/- and loxl1-/- zebrafish compared with the wildtype (P < 0.01 for all Bonferroni post-hoc analyses). The zonule of loxl1-/- zebrafish appeared stretched, ragged and torn, with isolated fibers also detected. The particles in loxl1-/- zebrafish were more numerous (counts: 92.33 ± 10.02/100 μm2 vs 58.33 ± 5.03/100 μm2 , P = 0.006), but smaller in size (diameter: 0.21 ± 0.03 μm vs 0.43 ± 0.04 μm, P = 0.002) compared with those in loxl1+/- . Transmission electron microscopy revealed thinning or even loss of elastic lamina in loxl1+/- Bruch's membrane (thickness of elastic lamina: 92.94 ± 18.19 nm in the wildtype vs 35.65 ± 14.76 nm in loxl1+/- , P = 0.003). The breakage of Bruch's membrane was observed in loxl1-/- .
Conclusions The loxl1-/- zebrafish is a promising animal model of XFS zonular pathology. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping