AN ANIMAL MODEL OF CONGENITAL HYPOTHYROIDISM

甲状腺激素（T3，T4）发挥关键作用，但只是部分 在发展和维持正常 外周和中枢神经系统功能。 临床上， 甲状腺功能减退症的精神和神经影响， 甲状腺机能亢进症包括：智力迟钝，学习障碍， 耳聋、视神经病变、谵妄、痴呆、精神病， 偏执和抑郁 临床表现 可能与甲状腺介导的神经递质变化有关 调节和脑基因表达。 胎儿期甲状腺激素缺乏， 是克汀病综合征的基础， 先天性甲状腺功能减退症，这是一个原因， 发育迟缓、学习障碍和运动残疾。 的 每5000名新生儿中就有1名出现综合征。 对我们理解 病理生理学和人类状况的治疗，动物 先天性甲状腺功能减退症的模型是必要的。 目前提出的一系列研究的目的是利用 一种跨学科的方法来确定近交系的效用， 小鼠先天性甲状腺功能减退症动物模型 老鼠. 该模型与人类胎儿具有特别的相关性。 甲状腺疾病，并可能帮助我们了解更多关于治疗， 精神发育迟滞的病因和基质以及最初的 甲状腺激素对发育中的 个脑袋 具体目标是：1）表征行为， 神经解剖学（特别是在大脑皮层层I-IV）和 hyt/hyt中存在的甲状腺和激素差异 甲状腺功能减退小鼠胎儿和新生儿相对于正常小鼠 2）选择和分离几个小鼠脑， 在甲状腺激素分泌过程中受甲状腺激素调节的mRNA 胎鼠甲状腺发生后的宫内期 功能

Thyroid hormones (T3,T4) play a critical but only partially understood role in the development and maintenance of normal peripheral and central nervous system function. The clinical, psychiatric, and neurological effects of hypothyroidism and hyperthyroidism include: mental retardation, learning disability, deafness, optic neuropathy, delirium, dementia, psychosis, paranoid ideation, and depression. The clinical manifestations may be related to thyroid mediated changes in neurotransmitter regulation and brain gene expression. Deficiency of thyroid hormone during intrauterine life and subsequent to birth underlies the syndrome of cretinism or congenital hypothyroidism, which is a cause of mental retardation, impaired learning and motor disability. The syndrome occurs in 1 in 5000 births. For our understanding of the pathophysioloby and treatment of the human condition, an animal model of congenital hypothyoidism is essential. The purpose of the present proposed series of studies is to utilize an interdisciplinary approach to determine the utility of an inbred mouse animal model of congenital hypothyroidism, the hyt/hyt mouse. This model has particular relevance to human fetal thyroid disorders and may help us learn more about the treatment, etiology, and substrate of mental retardation as well as the initial and pervasive effects of thyroid hormones on the developing brain. The specific aims are: 1) To characterize the behavioral, neuroanatomical (particularly in cerebral cortex layers I-IV) and thyroid gland and hormone differences that exist in the hyt/hyt hypothyroid mouse fetus and neonate relative to normal mouse offspring; and 2) To choose and isolate, several mouse brain mRNAs which are regulated by thyroid hormone(s) during the intrauterine period following the onset of fetal mouse thyroid function.