Loss of Usher II Proteins in Mice Does Not Affect Photoreceptor Ultrastructure

Usher syndrome is characterized by both vision and hearing loss. Mutations in three genes, USH2A, ADGRV1, and WHRN, lead to Usher syndrome Type II, in which the onset of vision loss usually takes place after puberty. Mouse models of Usher syndrome Type II have an incredibly mild retinal phenotype that typically begins after ~1-2 years of age and, therefore, do not fully represent the pathology in human patients. Both USH2A (also known as Usherin) and ADGRV1 (also known as USH2C or GPR98) are transmembrane proteins containing large extracellular domains. In this study, we questioned whether the relatively mild phenotype of USH2A and ADGRV1 mutant mouse models may arise from a functional redundancy between these two proteins. We generated a double knockout (Ush2a^-/-; Adgrv1^-/-) mouse and analyzed its retinal ultrastructure. We found no notable morphological defects in photoreceptor inner segments, connecting the cilia and outer segments of these mice at 1 month of age. These data indicate that functional redundancy between USH2A and ADGRV1 does not underlie the mild and late-onset retinal pathology observed in mice as compared to the aggressive nature of vision loss observed in corresponding human patients.