Rab28-flox Mouse

Rab28, a member of the RAS oncogene family, is a farnesylated, small GTPase. It is involved in multiple cellular processes. In the retina, it plays a crucial role in outer segment phagocytosis (OSP) and the visual cycle. It is also associated with ciliary function, as it negatively regulates extracellular vesicle shedding in cilia [2]. In addition, Rab28 is involved in GLUT4 trafficking in muscle cells and adipocytes, and may participate in NF-κB nuclear transport in endothelial cells [3,6]. Zebrafish and mouse models have been valuable for studying Rab28 [1,4,5,7].

In gene-knockout models, Rab28-deficient zebrafish show defective outer segment shedding in cone photoreceptors without retinal degeneration up to 12 months post-fertilization [5]. In Rab28 -/- mice, there is a recapitulation of human cone-rod dystrophy features, with reduced cone and rod electroretinography responses, progressive retina degeneration, and almost absent cone phagosomes [7]. In human patients, null and hypomorphic alleles of RAB28 cause autosomal recessive cone-rod dystrophy (arCORD), and a missense mutation prevents its localization to the primary cilium [1,8].

In conclusion, Rab28 is essential for normal function in the retina, especially in cone-related processes like OSP and maintaining photoreceptor and RPE homeostasis. Gene-knockout mouse models have been instrumental in revealing its role in cone-rod dystrophy, providing insights into the disease mechanism and potential gene therapy strategies for RAB28-associated CORD [1,4,7,9].