Effect of retinol dehydrogenase gene transfer in a novel rat model of Stargardt disease.
ABCA4
NADPH
Stargardt disease
retinoid toxicity
retinol dehydrogenase
transgenic rat
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
25
08
2021
received:
30
11
2020
accepted:
03
09
2021
entrez:
2
10
2021
pubmed:
3
10
2021
medline:
16
11
2021
Statut:
ppublish
Résumé
Dysfunction of the ATPase-binding Cassette Transporter protein (ABCA4) can lead to early onset macular degeneration, in particular to Stargardt disease. To enable translational research into this form of blindness, we evaluated the effect of Cas9-induced disruptions of the ABCA4 gene to potentially generate new transgenic rat models of the disease. We show that deletion of the short exon preceding the second nucleotide-binding domain is sufficient to drastically knock down protein levels and results in accumulation of retinoid dimers similar to that associated with Stargardt disease. Overexpression of the retinol dehydrogenase enzymes RDH8 and RDH12 can to a limited extent offset the increase in the bisretinoid levels in the Abca4
Identifiants
pubmed: 34599778
doi: 10.1096/fj.202002525RRR
doi:
Substances chimiques
ATP-Binding Cassette Transporters
0
Abca4 protein, rat
0
Vitamin A
11103-57-4
NADP
53-59-8
Alcohol Oxidoreductases
EC 1.1.-
retinol dehydrogenase
EC 1.1.1.105
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21934Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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