AN ANIMAL MODEL OF CONGENITAL HYPOTHYROIDISM

甲状腺激素（T3,T4）起关键作用，但只是部分作用

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.