Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature.
Invest Ophthalmol Vis Sci
; 61(2): 39, 2020 02 07.
Article
em En
| MEDLINE
| ID: mdl-32097476
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasos Retinianos
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Proteínas de Ligação a DNA
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Vitreorretinopatias Exsudativas Familiares
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2020
Tipo de documento:
Article