Year: 2025
Type: article
Abstract: The ABCA4 protein plays an essential role in mammalian vision, ensuring the correct localization of all-trans-retinal within the visual cycle. Mutations in the ABCA4 gene are responsible for the juvenile maculopathy, Stargardt disease (STGD1). We investigated the most common variant underlying STGD1 phenotype in a rat model carrying the ortholog to the human c.5882G > A/p.(Gly1961Glu) (G1961E) in ABCA4. While the pathogenicity of this variant has recently been questioned, we examine here whether the ortholog rat variant is associated with vitamin A toxicity in the retina. By crossing the rat line with a rat line deficient in ABCA4 protein, we reveal a more pathogenic phenotype in line with compound heterozygosity, making the model suitable for testing of gene, cell and pharmacological therapies.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddaf057
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Awards: G1190173965, G1337935431, G1394482618, Development of breakthrough Genome editing technologies, G2450198060, G2558356852, G2634253800, G381665449, Immunothérapies Grand Ouest, G4683787787, G5607072047, G5802621812, Mutualised Digital Spaces for FAIR data in Life and Health Science, Institut français de bioinformatique, G7240651115, G8234668411
OpenAlex ID: W4409739028