Rho KO Mouse

he Rhodopsin gene (RHO) is predominantly expressed in rod photoreceptor cells of the retina, where it encodes rhodopsin, a G protein-coupled receptor crucial for scotopic vision. Functioning as a light-sensitive pigment, rhodopsin initiates phototransduction upon photon absorption, triggering neural signaling to the brain ^[1]. Restricted to rod cells within the neural retina, mutations in RHO are a major etiological factor in inherited retinal degenerations, notably autosomal dominant retinitis pigmentosa (RP), characterized by progressive rod photoreceptor dysfunction leading to night blindness and tunnel vision ^[2-3]. Furthermore, RHO mutations are implicated in congenital stationary night blindness (CSNB) and Leber congenital amaurosis (LCA) ^[4]. Studies have shown that homozygous Rho knockout (KO) mice, due to the absence of functional rhodopsin protein, exhibit failure of rod outer segment formation or rapid degeneration, leading to severe retinal degeneration and vision loss early after birth. Heterozygous Rho KO mice, on the other hand, display slower, progressive retinal degeneration and functional decline ^[5-6]. Therefore, Rho KO mice can model human retinal diseases caused by complete loss of RHO function, such as certain autosomal recessive retinitis pigmentosa (arRP) or Leber congenital amaurosis (LCA), but are not suitable for modeling the most common autosomal dominant retinitis pigmentosa (adRP) caused by RHO mutations (e.g., the toxic protein produced by the P23H mutation) ^[7].

The Rho KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Rho gene (the homolog of the human RHO gene) in mice. The validation data shows that this model exhibits significant thinning of the outer nuclear layer (ONL) of the retina and abnormalities in electroretinography (ERG), effectively mimicking human disease phenotypes. Therefore, it can be used to study the pathogenic mechanisms of retinitis pigmentosa and congenital stationary night blindness, as well as for the research and development of related therapeutic interventions.