Deafness is a major health problem, affecting 1 in 800 children and a large part of the aging population. Many forms of deafness are of genetic origin and affect hair cells, the mechanosensors for sound in the inner ear. Several genes that are linked to deafness are expressed not only in hair cells, but in many other cell types. Hair cells, however, express specific isoforms of some of these genes as a result of cell-type specific splicing events. The long term objective of my application is to elucidate the importance of alternative splicing in regulating the cell-type specific function of genes in hair cells. Therefore, I propose to study the hair cell specific alternative splicing of Cdh23, a gene which has been linked to deafness in humans and mice. The central hypothesis of this application is that alternative splicing of the CDH23 cytoplasmic domain regulates its function in hair cells. To test this hypothesis, I will use single cell PCR to determine which of the two alternatively spliced variants of the CDH23 cytoplasmic domain are expressed in hair cells at different developmental stages. I will also analyze hair cell development and function in mice genetically modified to express one of the two CDH23 splice variants. Taken together, the findings are expected to provide insights into the expression pattern and function of CDH23 isoforms in hair cells. ? ? ?
