PUBLICATION
Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature
- Authors
- Karjosukarso, D.W., Ali, Z., Peters, T.A., Zhang, J.Q.C., Hoogendoorn, A.D.M., Garanto, A., van Wijk, E., Jensen, L.D., Collin, R.W.J.
- ID
- ZDB-PUB-200226-11
- Date
- 2020
- Source
- Investigative ophthalmology & visual science 61: 39 (Journal)
- Registered Authors
- Collin, Rob, Hoogendoorn, Anita, Karjosukarso, Dyah, van Wijk, Erwin
- Keywords
- none
- MeSH Terms
-
- Animals
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/physiology*
- Familial Exudative Vitreoretinopathies*/genetics
- Familial Exudative Vitreoretinopathies*/physiopathology
- Mutation, Missense
- Retinal Vessels/pathology*
- Zebrafish
- PubMed
- 32097476 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Karjosukarso, D.W., Ali, Z., Peters, T.A., Zhang, J.Q.C., Hoogendoorn, A.D.M., Garanto, A., van Wijk, E., Jensen, L.D., Collin, R.W.J. (2020) Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature. Investigative ophthalmology & visual science. 61:39.
Abstract
Purpose Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease in which the retinal vasculature is affected. Patients with FEVR typically lack or have abnormal vasculature in the peripheral retina, the outcome of which can range from mild visual impairment to complete blindness. A missense mutation (p.His455Tyr) in ZNF408 was identified in an autosomal dominant FEVR family. Little, however, is known about the molecular role of ZNF408 and how its defect leads to the clinical features of FEVR.
Methods Using CRISPR/Cas9 technology, two homozygous mutant zebrafish models with truncated znf408 were generated, as well as one heterozygous and one homozygous missense znf408 model in which the human p.His455Tyr mutation is mimicked.
Results Intriguingly, all three znf408-mutant zebrafish strains demonstrated progressive retinal vascular pathology, initially characterized by a deficient hyaloid vessel development at 5 days postfertilization (dpf) leading to vascular insufficiency in the retina. The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf.
Conclusions Together, our data demonstrate an important role for znf408 in the development and maintenance of the vascular system within the retina.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping