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The Thrb gene (Nr1a2), encoding thyroid hormone receptor β (TRβ), is one of two thyroid hormone receptor genes in the genome of vertebrate species. The other gene, Thra (Nr1a1), encodes the related thyroid hormone receptor TRα1 (see separate entry in TFe). These genes were initially identified by their homology to the avian retroviral oncogene v-erbA, which encodes a mutated form of chicken TRα1. TRβ is a ligand-regulated nuclear receptor and controls target gene expression in response to stimulation by thyroid hormone (T3). TRβ has the typical domain structure of a nuclear receptor with a central DNA binding domain consisting of a double zinc finger and a C-terminal ligand binding domain. TRβ has a variable N-terminal domain that differs between TRβ1 and TRβ2 isoform products of the gene. The N terminus may contribute to dimerization, DNA recognition or cofactor binding properties of the receptor. TRβ can bind to target DNA sites as a homodimer or heterodimer with retinoid X receptors (RXR) or more weakly as a monomer. TRβ can bind to DNA in the absence of ligand and therefore has the potential to mediate both T3-dependent and T3-independent transcriptional regulation of gene expression. On a typical positive-response gene, T3 stimulates a conformational change in TRβ that dissociates corepressors and allows recruitment of coactivators to form an activating complex that stimulates transcription.
The Thrb gene controls a range of endocrine and sensory functions in mouse models. Mutations in human THRB are associated with the syndrome of resistance to thyroid hormone (see separate entry for human THRB in TFe). Targeted mutagenesis shows that Thrb mediates the feedback control of the hypothalamic-pituitary-thyroid axis that determines thyroid hormone levels in the circulation. Thrb is also required for the development of the auditory system and of the cone photoreceptors that mediate colour visual function. In addition, Thrb mediates the major responses of the liver to T3.