ABCA4 Antibody

Overview of ABCA4 Antibody

The ABCA4 antibody is a polyclonal antibody targeting the ABCA4 protein, encoded by the ABCA4 gene. This protein is exclusively expressed in retinal photoreceptors and retinal pigment epithelium (RPE) cells, where it facilitates the transport of retinoid-phospholipid complexes to prevent toxic bisretinoid accumulation .

Development and Characterization

ABCA4 antibodies are validated through immunofluorescence, immunoblotting, and functional assays. For example:

• Immunofluorescence: Localizes ABCA4 to photoreceptor outer segments and RPE cells in wild-type mice, absent in Abca4^−/− models .

• Quantitative Immunoblotting: ABCA4 levels in RPE cells are ~1% of those in neural retina homogenates .

Table 1: ABCA4 Expression Levels in Mouse Tissues

Research Applications

ABCA4 antibodies are pivotal in:

• Disease Modeling: Studying ABCA4 variants (e.g., p.Arg290Gln, p.Asn1588Tyr) linked to Stargardt disease, which reduce plasma membrane expression due to intracellular degradation .

• Therapeutic Development: Testing gene therapy vectors (e.g., dual AAV systems) to restore ABCA4 function in Abca4^−/− mice, reducing toxic A2E accumulation .

• Mechanistic Studies: Confirming ABCA4’s role in flipping N-retinylidene-PE across disc membranes to prevent bisretinoid formation .

A. Functional Rescue in Abca4^−/− Mice

• Dual AAV Vectors: Hybrid ABCA4 dual vectors reduced A2E autofluorescence by 40–60% in treated mice .

• RPE-Specific Expression: Transgenic mice expressing ABCA4 solely in RPE showed partial rescue of photoreceptor degeneration .

Variant-Specific Pathogenicity

• Trafficking-Deficient Variants: Missense variants (e.g., p.Cys1140Trp) decrease plasma membrane expression by 40–88%, reversible with proteasomal/lysosomal inhibitors .

• Promoter Haplotypes: H1 (c.-761C>A) increases ABCA4 luciferase activity by 30%, while H3 (c.-1086A>C) decreases it by 50% .

Table 2: Impact of ABCA4 Variants on Protein Localization

Therapeutic Potential

• Antisense Oligonucleotides (AONs): A lead 2’-MOE/PS AON rescued splicing defects caused by ABCA4 c.768G>T in retinal organoids, restoring protein expression .

• Small Molecule Correctors: Compounds targeting misfolded ABCA4 variants (e.g., p.Asn1588Tyr) improved trafficking in vitro .