Animal Models to Study Thyroid Hormone Action in Neurodevelopment

Abstract

This chapter introduces representative animal models currently used to study thyroid hormone-mediated development and functional maintenance of target organs. Particularly, the potential animal model for the research on thyroid hormone system in neurodevelopment is discussed. Several representatives are (1) congenital hypothyroid animals caused by thyroid dysgenesis or thyroid dyshormonogenesis, (2) thyroid hormone receptor (TR)-modified animals, and (3) thyroid hormone transport or metabolism-modified animals. TR is a nuclear hormone receptor, which acts as a ligand-regulated transcription factor. On thyroid hormone response element, liganded TR activates transcription of target gene, whereas unliganded TR represses the transcription. Thus, phenotype of TR knockout mouse is different from that of hypothyroid animal (low thyroid hormone level), in which unliganded TR actively represses the transcription. On the other hand, a human patient harboring mutant TR expresses a different phenotype depending on the function of mutated TR. To mimic this phenotype, knock-in mice harboring various mutated TR have been generated. In addition, recent human studies have shown that thyroid hormone transporters such as monocarboxylate transporter (MCT) 8 may play an important role in thyroid hormone-mediated brain development. However, MCT8 knockout mouse shows a different phenotype from that of a human patient. Although it is impossible to introduce the whole sets of model animal in thyroid and neurodevelopment research, this chapter may be helpful to understand an outline of this field.