Rdh8-KO Mouse

The RDH8 gene encodes a member of the short-chain dehydrogenase/reductase (SDR) family known as retinol dehydrogenase 8 (or photoreceptor-specific all-trans-retinol dehydrogenase). This protein is primarily expressed in the retina, specifically localized to the outer segments of rod and cone photoreceptor cells, where it acts as the major dehydrogenase responsible for clearing all-trans-retinal. Its primary function is to catalyze the NADPH-dependent reduction of all-trans-retinal to all-trans-retinol, a critical and rate-limiting step in the visual (retinoid) cycle that prevents the accumulation of toxic retinal aldehydes ^[1]. While RDH8 works alongside RDH12 and ABCA4 to maintain retinal health, its dysfunction is significantly linked to Stargardt macular dystrophy (specifically STGD5) and Age-Related Macular Degeneration (AMD). Recent clinical research has identified specific biallelic splicing variants in RDH8 that lead to progressive macular atrophy, and studies in Abca4^-/-Rdh8^-/- animal models continue to reveal how the failure of this gene triggers inflammatory stress responses and ferroptosis (a type of programmed cell death) in the neural retina ^[2].

Rdh8-KO mice are a gene knockout (KO) model in which exons 1-6 of the Rdh8 gene in mice have been knocked out using gene-editing technology. This model can be used to study the pathogenic mechanisms of diseases such as Stargardt macular dystrophy type 5 (STGD5) and age-related macular degeneration (AMD), as well as for the development of relevant treatment methods.