B6-Rpe65 R44X Mouse

Leber congenital amaurosis (LCA) is a group of inherited retinal diseases accompanied by severe visual impairment. The main symptoms of this disease are vision loss at birth or within a few months after birth, nystagmus, and weakened or absent light reflexes of rods and cones. Approximately 16% of LCA cases are caused by mutations in the RPE65 gene. In visual cells, vitamin A aldehyde (retinal) combines with opsin to form visual pigments. After vitamin A aldehyde absorbs light, it is isomerized to all - trans - retinal, which causes a conformational change in rhodopsin and initiates nerve impulses to the brain, thus forming vision. During the decomposition and resynthesis of rhodopsin, a portion of vitamin A aldehyde is consumed and is mainly replenished by vitamin A (retinol) in the blood.The retinoid isomerase encoded by the RPE65 gene is present in the retinal pigment epithelial cells (RPE) of the retina. The RPE65 protein plays a crucial role in the visual process. It participates in the conversion of vitamin A to vitamin A aldehyde and the regeneration of retinal photoreceptor pigments, so it is a key molecule for the conversion and transmission of light signals in the retina^[1].

Mutations in the RPE65 gene can lead to further degeneration of the neural retina and RPE cells, resulting in irreversible blindness. Multiple allelic mutations of RPE65 have been found to damage optic nerve cells and cause type II Leber congenital amaurosis (LCA2) and early - onset severe retinal atrophy (EOSRD), ultimately leading to complete blindness^[1-3].

This model is a mouse Rpe65 gene point - mutation model. Using gene - editing technology, a p.R44*(CGA to TGA) point mutation was introduced into the mouse Rpe65 gene, which led to abnormal expression of the mouse Rpe65 protein. This caused phenotypes such as damage to RPE cell function, apoptosis of photoreceptor cells, disordered arrangement of rod outer segment membrane discs, and extinction of rod waveforms, resulting in severe retinal degeneration.