PUBLICATION
Znf469 Plays a Critical Role in Regulating Synthesis of ECM: A Zebrafish Model of Brittle Cornea Syndrome
- Authors
- Bao, J., Yu, X., Ping, X., Shentu, X., Zou, J.
- ID
- ZDB-PUB-230601-37
- Date
- 2023
- Source
- Investigative ophthalmology & visual science 64: 2929 (Journal)
- Registered Authors
- Zou, Jian
- Keywords
- none
- Datasets
- GEO:GSE225418
- MeSH Terms
-
- Animals
- Cornea
- Eye Abnormalities*/genetics
- Skin Abnormalities*/genetics
- Transcription Factors/genetics
- Zebrafish
- PubMed
- 37256609 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Bao, J., Yu, X., Ping, X., Shentu, X., Zou, J. (2023) Znf469 Plays a Critical Role in Regulating Synthesis of ECM: A Zebrafish Model of Brittle Cornea Syndrome. Investigative ophthalmology & visual science. 64:2929.
Abstract
Purpose Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder characterized by extreme thinning and fragility of the cornea, and mutations in ZNF469 cause BCS-1. We aimed to establish a znf469 mutant zebrafish line to explore its roles and possible pathogenic mechanism in cornea development and disorder.
Methods znf4694del/4del mutant zebrafish was generated using the CRISPR/Cas9 technology. Transmission electron microscopy (TEM) was performed to examine the phenotype of the cornea in different developmental stages. RNA sequencing and quantitative real-time polymerase chain reaction were used to reveal the molecular mechanism.
Results Macroscopically, homozygous znf469 mutant zebrafish larvae exhibited a curved body from 72 hours postfertilization, similar to kyphoscoliosis, and a noninflated swimbladder at 7 days postfertilization (dpf). TEM revealed an extreme reduction of corneal stroma thickness in homozygous znf469 mutant zebrafish in both the central and peripheral cornea from the early development stage. RNA-sequencing analysis demonstrated that the znf469 mutation leads to the decreased synthesis of various extracellular matrix (ECM) components, such as collagens and proteoglycans, but increased synthesis of 26S proteasome family members.
Conclusions The results of our work indicate that znf469 is a critical gene that, as a widely considered transcription factor, may regulate the synthesis and degradation of a large number of ECM components that play an important role in corneal development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping