Role of GATA3 in the cochlear-vestibular ganglion

描述(申请人提供)：人类GAT A3基因突变导致出生时出现感觉神经性耳聋，由于在人类或小鼠中，发育中的内耳中没有发现GAT A3的目标基因，因此这种耳聋的最终原因尚不清楚。转录因子GAT A3在耳蜗处表达，但在耳蜗神经节的前庭细胞中不表达。据推测，GATA3定义了耳蜗命运，并调节了指定细胞类型的基因的表达，包括在耳朵和中枢听觉系统之间形成特定的连接。为了测试GATA3是否对神经节神经元的发育和功能是必需的，我们将使用Cre-lox技术从耳蜗前庭神经节细胞中特异性地删除GATA3。将使用各种标记神经元及其过程的技术来研究GATA3缺失的细胞后果；各种分子标记的变化将进一步有助于定义GATA3的S作用。使用行为分析和基本电生理学，观察到的任何变化都将与对听力和平衡的影响相关。

DESCRIPTION (provided by applicant): 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.