The RPE65-Deficient Mouse as a Model for RPE65-Associated Leber’s Congenital Amaurosis and Related Disorders

Abstract

The retinal pigment epithelium (RPE)-specific protein RPE65 has been speculated to play a role in the vitamin A metabolism of the outer retina. Recently, mutations in the human RPE65 gene have been associated with Leber’s congenital amaurosis, a disorder characterized by blindness at birth, and autosomal recessive childhood-onset severe retinal dystrophies. We have developed an RPE65-deficient mouse and have described its phenotype. The RPE65-deficient mouse phenotype parallels that of the human disorders. This phenotype can be explained by a disruption of the RPE visual cycle causing a lack of 11-cis-retinal chromophore. Consequently, it is feasible to use this mouse as a model to test possible therapies for the human diseases.