WITHDRAWN: Retinal Phenotypes and Single-cell Sequencing Analysis of Ush2a Knockout Mice

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Ophthalmology

Background:

• Usher syndrome is a rare genetic disorder causing sensorineural hearing loss and retinitis pigmentosa-induced vision loss.
• The precise mechanisms driving retinal degeneration in Usher syndrome remain largely unelucidated.
• A robust animal model is crucial for understanding Usher syndrome pathogenesis.

Purpose of the Study:

• To develop and characterize a novel Ush2a knockout mouse model for Usher syndrome research.
• To investigate the early auditory and retinal functional and morphological changes in Ush2a-deficient mice.
• To construct an initial single-cell regulatory map of the retina in the Ush2a knockout model.

Main Methods:

• CRISPR/Cas9 gene editing was employed to generate the Ush2a knockout mouse model.
• Auditory brainstem response, electroretinography, and HE staining were used for phenotypic analysis.
• Retinal single-cell RNA sequencing was performed to analyze cellular expression profiles.

Main Results:

• The Ush2a knockout mouse model was successfully established.
• Auditory functional impairment was detected in Ush2a knockout mice by 6 months of age.
• No significant morphological or electrophysiological retinal phenotypes were observed in Ush2a knockout mice up to 20 months.

Conclusions:

• The Ush2a knockout mouse model exhibits early-onset auditory deficits.
• Retinal degeneration may not be an early or primary phenotype in this specific Ush2a mouse model.
• Single-cell RNA sequencing provided insights into Ush2a-related molecular mechanisms and retinal cell regulatory programs during development.