Rs1 KO Mouse

The RS1 gene (Retinoschisin 1) is primarily expressed in photoreceptor inner segments (rods and cones) and bipolar cells of the retina, with transcription controlled by factors like CRX. It encodes the secreted protein retinoschisin, a 224-amino-acid protein that assembles into a homo-octameric complex featuring a highly conserved discoidin domain ^[1]. Its main function is thought to be in cell-cell adhesion and the maintenance of retinal structure and the photoreceptor-bipolar synaptic structure, potentially through interactions with the plasma membrane, including the Na/K-ATPase ^[2]. Over 196 different RS1 gene mutations have been associated with X-linked retinoschisis (XLRS), indicating a large mutational spectrum and high phenotypic variability. For instance, these mutations can result in a loss of RS1 protein function, the secretion of a non-functional RS1 protein, or a functional protein that remains trapped inside the cell (intracellularly) ^[3]. When a pathogenic loss-of-function mutation occurs in the RS1 gene, it triggers XLRS—a common type of hereditary macular degeneration in males—characterized by an abnormal splitting of the inner retinal layers. This pathological change ultimately leads to progressive retinal degeneration, gradual vision loss that cannot be corrected with glasses, and eventually, blindness ^[4].

The Rs1 KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Rs1 gene (the homolog of the human RS1 gene) in mice. It can be used to study the pathogenic mechanisms of X-linked retinoschisis (XLRS), as well as for the development of related therapeutic interventions.