Thyroid hormone and the auditory system

甲状腺激素是神经系统发育所必需的。哺乳动物胎儿或新生儿在发育早期缺乏甲状腺激素会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，尽管甲状腺激素对听力的重要性，但其在听觉系统发育中的作用尚不完全清楚。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。进展:

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.