Retinal Phenotypes and Single-cell Sequencing Analysis of Ush2a Knockout Mice.

Abstract

Usher syndrome is a rare autosomal recessive genetic disorder that primarily affects both vision and hearing, manifesting as sensorineural hearing loss and progressive vision loss caused by retinitis pigmentosa. The pathogenesis of retinal degeneration in Usher syndrome is still largely unknown. In this study, a novel Ush2a knockout mouse model was successfully constructed using CRISPR/Cas9 technology. Auditory brainstem response tests, electroretinography, HE staining and retinal single-cell RNA sequencing were performed in Ush2a knockout and wild-type mice. Initial phenotypic observations of Ush2a knockout mice revealed auditory functional impairment in Ush2a knockout mice at 6 months, but no apparent morphological and electrophysiological phenotypes in the retina were found at 20 months. Single-cell RNA sequencing was performed to understand the expression profiles of various cell types in the retina of Ush2a knockout mice, and an initial single-cell regulatory map was constructed. Our study initially elucidated the possible mechanisms of Ush2a-related molecules and the potential regulatory programs of cells during development.