Role of GATA3 in the cochlear-vestibular ganglion

描述（由申请人提供）：GAT A3基因中的人类突变导致出生时存在的感音神经性耳聋，并且由于在人或小鼠中，尚未鉴定出发育中内耳中的GAT A3靶基因，因此该耳聋的最终原因未知。转录因子GATA 3在耳蜗中表达，但不在耳蜗-前庭神经节的前庭细胞中表达。据推测，GATA 3定义耳蜗的命运，并调节基因的表达，指定细胞类型，包括耳朵和中央听觉系统之间的特定连接的形成。为了测试GATA 3是否是神经节神经元发育和功能所必需的，将使用Cre-lox技术从耳蜗-前庭神经节细胞特异性地缺失GATA 3。将使用多种技术标记神经元及其过程来检查GATA 3丢失的细胞后果;各种分子标记物的改变将进一步帮助定义GATA 3的作用。观察到的任何变化都将与对听力和平衡的影响相关，使用行为测定和基本电生理学。

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.