*3.1. ABCA4*

Stargardt disease is an inherited macular dystrophy which affects one in 8,000–10,000 people. It is the most common inherited macular dystrophy and there is currently no cure. It results from mutations in the gene *ABCA4*. Mutations in *ABCA4* also result in cone–rod dystrophies and RP. ABCA4 is an ATP-dependent flippase expressed in the photoreceptor disc membrane and is necessary in the visual cycle for its transport of N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine out of the lumen into the cytoplasm [53].

A 1 bp insertion in *Abca4* was identified in a family group of Labrador retriever dogs resulting in a frameshift and premature stop codon [54]. This mutation causes a decrease in the mRNA transcript and the loss of the full-length protein. As seen in humans, there is an accumulation of lipofuscin in the RPE cells. Cone and rod photoreceptors both had abnormal function and were decreased in number in older affected dogs (10+ years). The development of a colony of these dogs as a model for therapy will have a substantial impact on the treatment of humans with Stargardt disease because mouse *Abca4*−/− models lack a phenotype [54,55]. The phenotype in the dog appears to be milder than that seen in human subjects, with *ABCA4* mutations reflecting species differences [56]. Early biomarkers of retinal changes in the affected dogs will facilitate the use of the *Abca4* mutant dog as a model for human Stargardt disease.
