Our long term objective is to understand the underlying molecular mechanisms involved in development of the mammalian auditory system. The specific goal of this application is to use molecular genetic techniques to isolate and characterize the mouse waltzer gene. Waltzer (v) is a recessive mutation characterized by congenital deafness, bi- directional circling behavior, and hyperactivity. The central hypothesis of this application is that waltzer is a mouse model for human hereditary deafness. Based on genetic map position, the v gene is located near and may be the same as two other deafness-related loci on mouse chromosome 10: a deafness modifier locus, mdfw, and a locus implicated in late onset progressive hearing loss, Ahl. Since v maps to a region of mouse Chromosome 10 that shares homology with a region of human chromosome 10 known to contain at least two deafness loci, USH1D and DFNB12, the human homologue of the v gene may be one of these deafness genes. Identification of the v gene will facilitate identification of the human homologue of waltzer. Once the human v gene is identified, its role in human hereditary deafness can be assessed. We will use molecular genetic techniques to accomplish four specific aims: 1) clone the mouse v gene, 2) clone the human v gene, 3) determine if the human v gene is responsible for Usher syndrome Type 1D, and 4) identify modifying loci that alter the waltzer phenotype. cloning of the v gene will identify a new gene that plays a role in auditory development and hearing impairment and may provide important insight into understanding human hereditary deafness.
Showing the most recent 10 out of 63 publications