Presenter: Kimberly Lerner
Mentors: Monte Westerfield and Jennifer Phillips, Biology
Poster: 42
Major: Biology
Usher syndrome is a hereditary disorder and the main cause of deaf-blindness. Patients diagnosed with Usher syndrome experience hearing loss and progressive blindness due to photoreceptor degeneration. The most common form of Usher syndrome is type 2A, which is caused by mutations in the USH2A gene. Although gene therapies for some forms of Usher syndrome are being actively researched, current gene replacement methods are not feasible for USH2A patients due to the large size of the USH2A gene. Zebrafish orthologues of Usher genes can be used as models of human Usher syndrome, and our research will contribute to the use of zebrafish as a model of USH2A. Three different mutations targeting different regions of the gene will be characterized in this study, with a specific focus on the ush2asa1881 mutant. Usherin forms a complex with other Usher type 2 proteins at the base of the connecting cilium in order to load ciliary cargo on this transport system between the inner and outer segments of the photoreceptor cells. We studied the co-localization of other known Usher proteins in the ush2asa1881 mutant background, to see if a mutant form of Usherin disrupted the normal localization of these other proteins. The accumulation of photoreceptor cell death in the retina over time leads to progressive vision loss in human USH2A patients. It may be difficult to see progressive retinal degeneration occur over the much shorter life span of the zebrafish, and mouse models of Usher syndrome have a mild retinal phenotype compared to the degree of vision loss that human patients experience. We devised a system that would challenge the retina to see if we could accelerate the damage that is normally accumulated over a longer period of time. Our findings will be useful in that we have created a functional zebrafish model of USH2A, and our results provide the foundation for a potential treatment though the protection of the retina.