| First Author | Tebbe L | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 972 |
| PubMed ID | 36810733 | Mgi Jnum | J:369719 |
| Mgi Id | MGI:7438755 | Doi | 10.1038/s41467-023-36431-1 |
| Citation | Tebbe L, et al. (2023) The usherin mutation c.2299delG leads to its mislocalization and disrupts interactions with whirlin and VLGR1. Nat Commun 14(1):972 |
| abstractText | Usher syndrome (USH) is the leading cause of combined deafness-blindness with type 2 A (USH2A) being the most common form. Knockout models of USH proteins, like the Ush2a(-/-) model that develops a late-onset retinal phenotype, failed to mimic the retinal phenotype observed in patients. Since patient's mutations result in the expression of a mutant protein and to determine the mechanism of USH2A, we generated and evaluated an usherin (USH2A) knock-in mouse expressing the common human disease-mutation, c.2299delG. This mouse exhibits retinal degeneration and expresses a truncated, glycosylated protein which is mislocalized to the photoreceptor inner segment. The degeneration is associated with a decline in retinal function, structural abnormalities in connecting cilium and outer segment and mislocaliztion of the usherin interactors very long G-protein receptor 1 and whirlin. The onset of symptoms is significantly earlier compared to Ush2a(-/-), proving expression of mutated protein is required to recapitulate the patients' retinal phenotype. |
