Endocrine Abstracts

T3 is essential for skeletal development and its actions are mediated by two nuclear receptors (TRs), with TR alpha (TRa) being functionally predominant in bone. The TRa1 isoform binds T3 with high affinity and activates target gene expression in response to hormone. TRa2, however, does not bind T3 or regulate transcription in response to hormone. Intriguingly, TRa2 is expressed at high levels from early in development in all tissues and is conserved in all mammals, although i...

T3-receptor alpha (TRa) is the predominant TR isoform in bone. To investigate its function, we analysed mice harbouring a dominant negative R384C mutation in TRa1 (TRa1m/+). The homozygous TRa1m/m mutation is lethal whereas heterozygotes are euthyroid displaying only transient postnatal hypothyroidism. Critically, dominant negative activity of the mutation is overcome by a 10-fold increase in T3, which is achieved by crossing TRa1m/+ mutants wi...