Animal models to study thyroid hormone action in cerebellum

Cerebellum. 2009 Jun;8(2):89-97. doi: 10.1007/s12311-008-0089-x. Epub 2009 Jan 7.

Abstract

Thyroid hormone plays a crucial role in the development and functional maintenance of the central nervous system including the cerebellum. To study the molecular mechanisms of thyroid hormone action, various animal models have been used. These are classified: (1) congenital hypothyroid animals due to thyroid gland dysgenesis or thyroid dyshormonogenesis, (2) thyroid hormone receptor (TR) gene-mutated animals, and (3) thyroid hormone transport or metabolism-modified animals. TR is a ligand-activated transcription factor. In the presence of ligand, it activates transcription of target gene, whereas it represses the transcription without ligand. 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, human patient harboring mutant TR expresses different phenotypes depending on the function of mutated TR. To mimic this phenotype, other animal models are 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 show different phenotypes from a human patient. This article introduces representative animal models currently used to study various aspects of thyroid hormone, particularly to study the involvement of the thyroid hormone system on the development and functional maintenance of the cerebellum.

Publication types

  • Review

MeSH terms

  • Animals
  • Cerebellar Diseases / genetics
  • Cerebellar Diseases / metabolism
  • Cerebellar Diseases / physiopathology
  • Cerebellum / growth & development*
  • Cerebellum / metabolism*
  • Cerebellum / physiopathology
  • Disease Models, Animal
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mice
  • Monocarboxylic Acid Transporters
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism
  • Symporters
  • Thyroid Diseases / complications
  • Thyroid Diseases / genetics
  • Thyroid Diseases / metabolism
  • Thyroid Gland / metabolism*
  • Thyroid Gland / physiopathology
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism*

Substances

  • Membrane Transport Proteins
  • Monocarboxylic Acid Transporters
  • Receptors, Thyroid Hormone
  • Slc16a2 protein, mouse
  • Symporters
  • Thyroid Hormones