Forward genetic analysis using OCT screening identifies Sfxn3 mutations leading to progressive outer retinal degeneration in mice

Understanding the mechanisms of retinal development and homeostasis is essential for the advancement of retinal regeneration strategies and conception of novel therapies for multifactorial retinal diseases. Forward genetic analysis allows for the unbiased identification of nonredundant genes involved in the generation and maintenance of retinal integrity. Here we combine a special forward genetics protocol, in which all mice in tested pedigrees have been pregenotyped at all mutant loci with a sensitive and reproducible retinal screening assay, optical coherence tomography. We show that this robust pipeline can detect subtle phenotype-genotype associations and characterize one of multiple novel associations. This approach will help discover new pathways and better define known pathways essential to retinal development and function.