Human Usher syndrome, the most frequent cause of deaf blindness, is characterized by congenital deafness, due to loss of sensory hair cells, and progressive retinal degeneration, due to retinitis pigmentosa. Although nine of the genes responsible for Usher syndrome and one genetic modifier gene have been identified to date, we still lack an understanding of the normal functions of these genes or what goes wrong in the disease. This is primarily because the ten known genes encode a surprisingly broad range of different types of proteins, all with multiple isoforms, and we currently lack animal models and tools to study their functions. Due to recent advances in zebrafish genetic technology, it is now possible to isolate mutations in any gene and easily produce transgenic animals with altered gene expression. This project will develop libraries of mutants, transgenics, and antibodies to characterize all the genes known to contribute to Usher syndrome. Together, these libraries will provide the first resource ever generated to dissect the distinct functions of the complete set of known genes that underlie a human disease.
Usher syndrome, the leading cause of deaf blindness, is a genetic disorder that affects tens of thousands of Americans. Mutations in any one of at least a dozen different genes can cause Usher syndrome, but the processes that lead to loss of hearing and vision are unknown. This project will develop a complete resource of animal models and tools necessary to understand the molecular and cellular biology of Usher syndrome.
| Blanco-Sánchez, Bernardo; Clément, Aurélie; Fierro Jr, Javier et al. (2018) Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins. Cell Rep 25:1281-1291.e4 |
| Beck, Bodo B; Phillips, Jennifer B; Bartram, Malte P et al. (2014) Mutation of POC1B in a severe syndromic retinal ciliopathy. Hum Mutat 35:1153-62 |
| Blanco-Sánchez, Bernardo; Clément, Aurélie; Fierro Jr, Javier et al. (2014) Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis. Dis Model Mech 7:547-59 |
