Thyroid hormone and the auditory system

甲状腺激素是神经系统发育所必需的。 在哺乳动物胎儿或新生儿的早期发育中缺乏甲状腺激素可导致智力迟钝和其他神经缺陷，包括耳聋。 听力是受甲状腺激素控制的最敏感的功能之一，尽管这种激素对听力很重要，但它在听觉系统发育中的作用还不完全清楚。 该项目的目标是阐明甲状腺激素在听觉系统中的功能，并确定介导这些功能的基因。 进度： 1. 对Thra甲状腺激素受体基因受体中具有新突变的小鼠品系的研究揭示了耳聋表型。 初步数据表明，耳蜗表型不同于先前与Thrb基因突变相关的表型，表明Thra和Thrb基因在听力发育中可能具有独立功能（与S-Y博士合作）。Cheng，NCI，Matt Kelley博士，NIDCD）。 2. 最近的数据表明，编码脱碘酶（甲状腺激素代谢酶）的基因对听力很重要。 结果表明，在小鼠遗传模型中，编码激活酶和失活酶的不同脱碘酶基因的表达模式的改变会产生耳聋表型。 这些发现表明，这些酶在听觉系统的靶组织中非常重要，可以精确地改变甲状腺激素在何时何地触发听力的正确启动。 因此，甲状腺激素对听觉系统的作用包括内分泌和旁分泌两种控制成分。 3. 编码细胞外基质蛋白的基因在耳蜗基因的筛选中被检测到，这些基因可能在缺乏甲状腺激素受体的耳聋小鼠中异常表达。该emilin基因已被研究为位于听觉发育中甲状腺激素信号下游的候选基因。 来自小鼠模型的初步数据表明，emilin基因是正常听觉功能所必需的。

Thyroid hormone is necessary for the development of the nervous system. A lack of thyroid hormone in early development in the mammalian fetus or neonate can result in mental retardation and other neurological defects, including deafness. Hearing is one of the most sensitive functions that is subject to control by thyroid hormone yet despite the importance of this hormone for hearing, its actions in the development of the auditory system are incompletely understood. The goals of the project are to elucidate the functions of thyroid hormone in the auditory system and to identify the genes that mediate these functions. Progress: 1. Study of a mouse strain with a novel mutation in the Thra thyroid hormone receptor gene receptor has revealed a deafness phenotype. Preliminary data indicate a cochlear phenotype that differs from that previously associated with mutations in the Thrb gene, suggesting possible independent functions for the Thra and Thrb genes in the development of hearing (collaboration with Dr. S-Y. Cheng, NCI, Dr. Matt Kelley, NIDCD). 2. Recent data show that genes encoding deiodinases, thyroid hormone-metabolizing enzymes, are important for hearing. The results suggest that changing patterns of expression of distinct deiodinase genes encoding both activating and inactivating enzymes produce deafness phenotypes in mouse genetic models. The findings suggest that these enzymes are important within the target tissues of the auditory system for modifying precisely where and when thyroid hormone acts in triggering the correct onset of hearing. Thus, the action of thyroid hormone upon the auditory system incorporates both endocrine and paracrine components of control. 3. A gene encoding an extracellular matrix protein was detected in a screen for cochlear genes that may be abnormally expressed in deaf mice lacking a thyroid hormone receptor. This emilin gene has been studied as a candidate gene that lies downstream of the thyroid hormone signal in auditory development. Preliminary data from a mouse model suggest that the emilin gene is required for normal auditory function.