A human mutation in the GAT A3 gene results in sensorineural deafness present at birth and since, in man or mouse, no target genes of GAT A3 in the developing inner ear have been identified, the ultimate cause of this deafness is unknown. The transcription factor GAT A3 is expressed in the cochlear but not in the vestibular cells of the cochlear-vestibular ganglion. It is hypothesized that GATA3 defines the cochlear fate and regulates the expression of genes that specify cell type, including the formation of specific connections between the ear and the central auditory system. To test whether GAT A3 is necessary for ganglion neuron development and function, GATA3 will be deleted specifically from the cochlear-vestibular ganglion cells using Cre-lox technology. The cellular consequences of GATA3 loss will be examined using a variety of techniques to label neurons and their processes; alterations in various molecular markers will further help define GATA3's action. Any changes observed will be correlated with effects on hearing and balance, using behavioral assays and basic electrophysiology. ? ?
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