Thyroid hormone action: Insight from transgenic mouse models

Fredric E. Wondisford

Research output: Contribution to journalArticle

Abstract

Thyroid hormone receptors (TRs) are cellular homologues of the viral erythroblastic leukemia oncogene (v-erbA). TRs (c-crbA isoforms) are derived from two separate gene loci in mammals: α and β. Through a series of knockout experiments in mice in which one or several of the TR isoforms were deleted, it has been demonstrated that the TR-β isoforms control central regulation of thyroid-stimulating hormone. Of these isoforms, TR-β2 is the most important in mediating negative feedback control of the hypothalamic-pituitary-thyroid axis. Further analysis of TR knockout animals revealed, however, that they exhibited a much milder overall phenotype than hypothyroid animals, indicating that receptor loss was not equivalent to ligand loss in vivo. To understand this apparent paradox, we generated animals expressing a non-T3 binding receptor (Δ337T) from the TR-β allele. These mice displayed a complete hypothyroid phenotype, demonstrating that the unliganded TR mediates the effect of hypothyroidism. Because this mutant TR constitutively binds to nuclear coreprssors, it also suggests that this class of proteins is essential for mediating hypothyroidism in vivo.

Original languageEnglish (US)
Pages (from-to)215-220
Number of pages6
JournalJournal of Investigative Medicine
Volume51
Issue number4
StatePublished - Jul 2003
Externally publishedYes

Fingerprint

Thyroid Hormone Receptors
Thyroid Hormones
Transgenic Mice
Protein Isoforms
Animals
Hypothyroidism
erbA Genes
Phenotype
Mammals
Thyrotropin
Feedback control
Thyroid Gland
Leukemia
Genes
Alleles
Ligands
Feedback

Keywords

  • Resistance to thyroid hormone
  • Thyroid hormone receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Thyroid hormone action : Insight from transgenic mouse models. / Wondisford, Fredric E.

In: Journal of Investigative Medicine, Vol. 51, No. 4, 07.2003, p. 215-220.

Research output: Contribution to journalArticle

Wondisford, Fredric E. / Thyroid hormone action : Insight from transgenic mouse models. In: Journal of Investigative Medicine. 2003 ; Vol. 51, No. 4. pp. 215-220.
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